T cell - Knowledge (XXG)

1265:, and it becomes more difficult for it to activate in future. This mechanism prevents inappropriate responses to self, as self-peptides will not usually be presented with suitable co-stimulation. Once a T cell has been appropriately activated (i.e. has received signal one and signal two) it alters its cell surface expression of a variety of proteins. Markers of T cell activation include CD69, CD71 and CD25 (also a marker for Treg cells), and HLA-DR (a marker of human T cell activation). CTLA-4 expression is also up-regulated on activated T cells, which in turn outcompetes CD28 for binding to the B7 proteins. This is a checkpoint mechanism to prevent over activation of the T cell. Activated T cells also change their cell surface glycosylation profile. 513:β-selection is the first checkpoint, where thymocytes that are able to form a functional pre-TCR (with an invariant alpha chain and a functional beta chain) are allowed to continue development in the thymus. Next, positive selection checks that thymocytes have successfully rearranged their TCRα locus and are capable of recognizing MHC molecules with appropriate affinity. Negative selection in the medulla then eliminates thymocytes that bind too strongly to self-antigens expressed on MHC molecules. These selection processes allow for tolerance of self by the immune system. Typical naive T cells that leave the thymus (via the corticomedullary junction) are self-restricted, self-tolerant, and single positive. 40: 1383:(Caspase activation and recruitment domains) domains; that then binds TRAF6, which is ubiquitinated at K63. This form of ubiquitination does not lead to degradation of target proteins. Rather, it serves to recruit NEMO, IKKα and -β, and TAB1-2/ TAK1. TAK 1 phosphorylates IKK-β, which then phosphorylates IκB allowing for K48 ubiquitination: leads to proteasomal degradation. Rel A and p50 can then enter the nucleus and bind the NF-κB response element. This coupled with NFAT signaling allows for complete activation of the IL-2 gene. 768: 1442: 901:) differ from the other memory subsets in that they do not originate following a strong clonal expansion event. Thus, although this population as a whole is abundant within the peripheral circulation, individual virtual memory T cell clones reside at relatively low frequencies. One theory is that homeostatic proliferation gives rise to this T cell population. Although CD8 virtual memory T cells were the first to be described, it is now known that CD4 virtual memory cells also exist. 1719:

studies have suggested that it is possible to predict relapse of leukemia based on expression of inhibitory receptors PD-1 and TIM-3 by T cells. Many experiments and clinical trials have focused on immune checkpoint blockers in cancer therapy, with some of these approved as valid therapies that are now in clinical use. Inhibitory receptors targeted by those medical procedures are vital in T cell exhaustion and blocking them can reverse these changes.

551: 403:α-chain, signals are produced which cease rearrangement of the β-chain (and silence the alternate allele). Although these signals require the pre-TCR at the cell surface, they are independent of ligand binding to the pre-TCR. If the chains successfully pair a pre-TCR forms, and the cell downregulates CD25 and is termed a DN4 cell (CD25CD44). These cells then undergo a round of proliferation, and begin to re-arrange the TCRα locus during the 999:

recognition of peptide antigens in the context of the MHC molecule. Overall, there are three large populations of unconventional T cells: NKT cells, MAIT cells, and gammadelta T cells. Now, their functional roles are already being well established in the context of infections and cancer. Furthermore, these T cell subsets are being translated into many therapies against malignancies such as leukemia, for example.

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must be tested to make sure they work at all. First, the thymocytes attempt to create a functional beta chain, testing it against a 'mock' alpha chain. Then they attempt to create a functional alpha chain. Once a working TCR has been produced, the cells then must test if their TCR will identify threats correctly, and to do this it is required to recognize the body’s

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thought to belong to either the effector or central memory subtypes, each with their own distinguishing set of cell surface markers (see below). Subsequently, numerous new populations of memory T cells were discovered including tissue-resident memory T (Trm) cells, stem memory TSCM cells, and virtual memory T cells. The single unifying theme for all

1233:, like dendritic cells, B cells, and macrophages, to name a few. The peptides presented to CD8 T cells by MHC class I molecules are 8–13 amino acids in length; the peptides presented to CD4 cells by MHC class II molecules are longer, usually 12–25 amino acids in length, as the ends of the binding cleft of the MHC class II molecule are open. 1119:. In rabbits, sheep, and chickens, the number of γδ T cells can be as high as 60% of total T cells. The antigenic molecules that activate γδ T cells are still mostly unknown. However, γδ T cells are not MHC-restricted and seem to be able to recognize whole proteins rather than requiring peptides to be presented by MHC molecules on 1690:

encounter anti-inflammatory cytokines and pro-apoptotic proteins take over to protect the body from damage. Sepsis also carries high antigen load and inflammation. In this stage of sepsis T cell exhaustion increases. Currently there are studies aiming to utilize inhibitory receptor blockades in treatment of sepsis.

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role in tolerance of a graft mainly by depletion of alloreactive CD8 T cells. Several studies showed positive effect of chronic infection on graft acceptance and its long-term survival mediated partly by T cell exhaustion. It was also shown that recipient T cell exhaustion provides sufficient conditions for

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While during infection T cell exhaustion can develop following persistent antigen exposure after graft transplant similar situation arises with alloantigen presence. It was shown that T cell response diminishes over time after kidney transplant. These data suggest T cell exhaustion plays an important

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About 98% of thymocytes die during the development processes in the thymus by failing either positive selection or negative selection, whereas the other 2% survive and leave the thymus to become mature immunocompetent T cells. The thymus contributes fewer cells as a person ages. As the thymus shrinks

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cells can be a source of IL-10 and TGF-β and therefore they can play a role in T cell exhaustion. Furthermore, T cell exhaustion is reverted after depletion of Treg cells and blockade of PD1. T cell exhaustion can also occur during sepsis as a result of cytokine storm. Later after the initial septic

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T cell exhaustion can be triggered by several factors like persistent antigen exposure and lack of CD4 T cell help. Antigen exposure also has effect on the course of exhaustion because longer exposure time and higher viral load increases the severity of T cell exhaustion. At least 2–4 weeks exposure

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into the cytosol. Low calcium in the endoplasmic reticulum causes STIM1 clustering on the ER membrane and leads to activation of cell membrane CRAC channels that allows additional calcium to flow into the cytosol from the extracellular space. This aggregated cytosolic calcium binds calmodulin, which

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During cancer T cell exhaustion plays a role in tumor protection. According to research some cancer-associated cells as well as tumor cells themselves can actively induce T cell exhaustion at the site of tumor. T cell exhaustion can also play a role in cancer relapses as was shown on leukemia. Some

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after they encounter their cognate antigen within the context of an MHC molecule on the surface of a professional antigen presenting cell (e.g. a dendritic cell). Appropriate co-stimulation must be present at the time of antigen encounter for this process to occur. Historically, memory T cells were

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T cells are grouped into a series of subsets based on their function. CD4 and CD8 T cells are selected in the thymus, but undergo further differentiation in the periphery to specialized cells which have different functions. T cell subsets were initially defined by function, but also have associated

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on their cell surface and although the T cell antigen receptor can interact with at least a subset of these self pMHC, the T cell generally ignores these healthy cells. However, when these very same cells contain even minute quantities of pathogen derived pMHC, T cells are able to become activated

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Negative selection removes thymocytes that are capable of strongly binding with "self" MHC molecules. Thymocytes that survive positive selection migrate towards the boundary of the cortex and medulla in the thymus. While in the medulla, they are again presented with a self-antigen presented on the

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and constant region genes in an attempt to create a functional TCRβ chain. As the developing thymocyte progresses through to the DN3 stage (CD44CD25), the thymocyte expresses an invariant α-chain called pre-Tα alongside the TCRβ gene. If the rearranged β-chain successfully pairs with the invariant

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A thymocyte can only become an active T cell when it survives the process of developing a functional TCR. The TCR consists of two major components, the alpha and beta chains. These both contain random elements designed to produce a wide variety of different TCRs, but due to this huge variety they

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production. Optimal CD8 T cell response relies on CD4 signalling. CD4 cells are useful in the initial antigenic activation of naive CD8 T cells, and sustaining memory CD8 T cells in the aftermath of an acute infection. Therefore, activation of CD4 T cells can be beneficial to the action of CD8 T

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subtypes is that they are long-lived and can quickly expand to large numbers of effector T cells upon re-exposure to their cognate antigen. By this mechanism they provide the immune system with "memory" against previously encountered pathogens. Memory T cells may be either CD4 or CD8 and usually

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T cell exhaustion is a poorly defined or ambiguous term. There are three approaches to its definition. "The first approach primarily defines as exhausted the cells that present the same cellular dysfunction (typically, the absence of an expected effector response). The second approach primarily

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on MHC molecules, which reside on the surface of cortical epithelial cells. Only thymocytes that interact well with MHC-I or MHC-II will receive a vital "survival signal", while those that cannot interact strongly enough will receive no signal and die from neglect. This process ensures that the

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Regulatory T cells can develop either during normal development in the thymus, and are then known as thymic Treg cells, or can be induced peripherally and are called peripherally derived Treg cells. These two subsets were previously called "naturally occurring" and "adaptive" (or "induced"),

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represent some subsets of T cells that behave differently in immunity. They trigger rapid immune responses, regardless of the major histocompatibility complex (MHC) expression, unlike their conventional counterparts (CD4 T helper cells and CD8 cytotoxic T cells), which are dependent on the

203:. After migration to the thymus, the precursor cells mature into several distinct types of T cells. T cell differentiation also continues after they have left the thymus. Groups of specific, differentiated T cell subtypes have a variety of important functions in controlling and shaping the 1628:

defines as exhausted the cells that are produced by a given cause (typically, but not necessarily, chronic exposure to an antigen). Finally, the third approach primarily defines as exhausted the cells that present the same molecular markers (typically, programmed cell death protein 1 )."

1111:(γδ T cells) represent a small subset of T cells which possess a γδ TCR rather than the αβ TCR on the cell surface. The majority of T cells express αβ TCR chains. This group of T cells is much less common in humans and mice (about 2% of total T cells) and are found mostly in the gut 5645:

Liu L, Chang YJ, Xu LP, Zhang XH, Wang Y, Liu KY, Huang XJ (May 2018). "T cell exhaustion characterized by compromised MHC class I and II restricted cytotoxic activity associates with acute B lymphoblastic leukemia relapse after allogeneic hematopoietic stem cell transplantation".

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While in most cases activation is dependent on TCR recognition of antigen, alternative pathways for activation have been described. For example, cytotoxic T cells have been shown to become activated when targeted by other CD8 T cells leading to tolerization of the latter.

1127:γδ T cells recognize MHC class IB molecules. Human γδ T cells that use the Vγ9 and Vδ2 gene fragments constitute the major γδ T cell population in peripheral blood. These cells are unique in that they specifically and rapidly respond to a set of nonpeptidic phosphorylated 1036:. Once activated, these cells can perform functions ascribed to both helper and cytotoxic T cells: cytokine production and release of cytolytic/cell killing molecules. They are also able to recognize and eliminate some tumor cells and cells infected with herpes viruses. 428:

surviving thymocytes will have an 'MHC affinity' that means they can serve useful functions in the body, responding to MHC molecules to assist immune responses. The vast majority of developing thymocytes will not pass positive selection, and die during this process.

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Pekalski ML, García AR, Ferreira RC, Rainbow DB, Smyth DJ, Mashar M, Brady J, Savinykh N, Dopico XC, Mahmood S, Duley S, Stevens HE, Walker NM, Cutler AJ, Waldron-Lynch F, Dunger DB, Shannon-Lowe C, Coles AJ, Jones JL, Wallace C, Todd JA, Wicker LS (August 2017).

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and initiate immune responses. The ability of T cells to ignore healthy cells but respond when these same cells contain pathogen (or cancer) derived pMHC is known as antigen discrimination. The molecular mechanisms that underlie this process are controversial.

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molecules mature into CD8 "killer" cells. A thymocyte becomes a CD4 cell by down-regulating expression of its CD8 cell surface receptors. If the cell does not lose its signal, it will continue downregulating CD8 and become a CD4, both CD8 and CD4 cells are now

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Kjer-Nielsen L, Patel O, Corbett AJ, Le Nours J, Meehan B, Liu L, Bhati M, Chen Z, Kostenko L, Reantragoon R, Williamson NA, Purcell AW, Dudek NL, McConville MJ, O'Hair RA, Khairallah GN, Godfrey DI, Fairlie DP, Rossjohn J, McCluskey J (November 2012).

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molecules (positively selected CD4 cells must interact with these MHC class II molecules, thus APCs, which possess MHC class II, must be present for CD4 T-cell negative selection). Thymocytes that interact too strongly with the self-antigen receive an

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Woo SR, Turnis ME, Goldberg MV, Bankoti J, Selby M, Nirschl CJ, Bettini ML, Gravano DM, Vogel P, Liu CL, Tangsombatvisit S, Grosso JF, Netto G, Smeltzer MP, Chaux A, Utz PJ, Workman CJ, Pardoll DM, Korman AJ, Drake CG, Vignali DA (February 2012).

264:" response. For this reason, these regulatory T cells have also been called "suppressor" T cells. These same regulatory T cells can also be co-opted by cancer cells to prevent the recognition of, and an immune response against, tumor cells. 1703:

transfer. While there are data showing that induction of T cell exhaustion can be beneficial for transplantation it also carries disadvantages among which can be counted increased number of infections and the risk of tumor development.

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A critical step in T cell maturation is making a functional T cell receptor (TCR). Each mature T cell will ultimately contain a unique TCR that reacts to a random pattern, allowing the immune system to recognize many different types of

1339:); PI3K also acts on PIP2, phosphorylating it to produce phosphatidlyinositol-3,4,5-trisphosphate (PIP3). DAG binds and activates some PKCs. Most important in T cells is PKC-θ, critical for activating the transcription factors 798:

molecules, present on the surface of all nucleated cells. Cytotoxic T cells also produce the key cytokines IL-2 and IFNγ. These cytokines influence the effector functions of other cells, in particular macrophages and NK cells.

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Shi XL, de Mare-Bredemeijer EL, Tapirdamaz Ö, Hansen BE, van Gent R, van Campenhout MJ, Mancham S, Litjens NH, Betjes MG, van der Eijk AA, Xia Q, van der Laan LJ, de Jonge J, Metselaar HJ, Kwekkeboom J (September 2015).

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The second signal comes from co-stimulation, in which surface receptors on the APC are induced by a relatively small number of stimuli, usually products of pathogens, but sometimes breakdown products of cells, such as

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by about 3% a year throughout middle age, a corresponding fall in the thymic production of naive T cells occurs, leaving peripheral T cell expansion and regeneration to play a greater role in protecting older people.

374:. This process is essential in developing immunity to threats that the immune system has not encountered before, since due to random variation there will always be at least one TCR to match any new pathogen. 297:. The process of differentiation then proceeds to a common lymphoid progenitor (CLP), which can only differentiate into T, B or NK cells. These CLP cells then migrate via the blood to the thymus, where they 1147:) and corresponding mononucleotide conjugates, in addition to IPP and DMAPP. Plant cells produce both types of phosphoantigens. Drugs activating human Vγ9/Vδ2 T cells comprise synthetic phosphoantigens and 1631:

Dysfunctional T cells are characterized by progressive loss of function, changes in transcriptional profiles and sustained expression of inhibitory receptors. At first, cells lose their ability to produce

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Marusina AI, Ono Y, Merleev AA, Shimoda M, Ogawa H, Wang EA, Kondo K, Olney L, Luxardi G, Miyamura Y, Yilma TD, Villalobos IB, Bergstrom JW, Kronenberg DG, Soulika AM, Adamopoulos IE, Maverakis E (2017).

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A unique feature of T cells is their ability to discriminate between healthy and abnormal (e.g. infected or cancerous) cells in the body. Healthy cells typically express a large number of self derived

234:, to recruit other types of cells when mounting an immune response. A different population of T cells, the CD4+ T cells, function as "helper cells". Unlike CD8+ killer T cells, the CD4+ helper T (T 5080:

Wei Z, Li P, Yao Y, Deng H, Yi S, Zhang C, Wu H, Xie X, Xia M, He R, Yang XP, Tang ZH (July 2018). "Alpha-lactose reverses liver injury via blockade of Tim-3-mediated CD8 apoptosis in sepsis".

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Bianchini E, De Biasi S, Simone AM, Ferraro D, Sola P, Cossarizza A, Pinti M (March 2017). "Invariant natural killer T cells and mucosal-associated invariant T cells in multiple sclerosis".

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The T lymphocyte activation pathway: T cells contribute to immune defenses in two major ways; some direct and regulate immune responses; others directly attack infected or cancerous cells.

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exists as a complex of several proteins. The actual T cell receptor is composed of two separate peptide chains, which are produced from the independent T cell receptor alpha and beta (

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that regulate or assist the immune response. These cells can differentiate into one of several subtypes, which have different roles. Cytokines direct T cells into particular subtypes.

1640:, which is followed by the loss of high proliferative capacity and cytotoxic potential, and eventually leads to their deletion. Exhausted T cells typically indicate higher levels of 3706:

Janssen EM, Lemmens EE, Wolfe T, Christen U, von Herrath MG, Schoenberger SP (February 2003). "CD4+ T cells are required for secondary expansion and memory in CD8+ T lymphocytes".

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cells, which are thought to originate during an immune response and act by producing suppressive molecules. Tr1 cells are associated with IL-10, and Th3 cells are associated with

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Abbas AK, Benoist C, Bluestone JA, Campbell DJ, Ghosh S, Hori S, Jiang S, Kuchroo VK, Mathis D, Roncarolo MG, Rudensky A, Sakaguchi S, Shevach EM, Vignali DA, Ziegler SF (2013).

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bacterially-infected cells. MAIT cells can also be activated through MR1-independent signaling. In addition to possessing innate-like functions, this T cell subset supports the

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co-receptor. The newly arrived CLP cells are CD4CD8CD44CD25ckit cells, and are termed early thymic progenitor (ETP) cells. These cells will then undergo a round of division and

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de Mare-Bredemeijer EL, Shi XL, Mancham S, van Gent R, van der Heide-Mulder M, de Boer R, Heemskerk MH, de Jonge J, van der Laan LJ, Metselaar HJ, Kwekkeboom J (August 2015).

6254: 5033:"Frontline Science: Defects in immune function in patients with sepsis are associated with PD-1 or PD-L1 expression and can be restored by antibodies targeting PD-1 or PD-L1" 4933:

Boomer JS, To K, Chang KC, Takasu O, Osborne DF, Walton AH, Bricker TL, Jarman SD, Kreisel D, Krupnick AS, Srivastava A, Swanson PE, Green JM, Hotchkiss RS (December 2011).

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Haynes BF, Markert ML, Sempowski GD, Patel DD, Hale LP (2000). "The role of the thymus in immune reconstitution in aging, bone marrow transplantation, and HIV-1 infection".

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Halloran PF, Chang J, Famulski K, Hidalgo LG, Salazar ID, Merino Lopez M, Matas A, Picton M, de Freitas D, Bromberg J, Serón D, Sellarés J, Einecke G, Reeve J (July 2015).

2809:"CD4+ virtual memory: Antigen-inexperienced T cells reside in the naïve, regulatory, and memory T cell compartments at similar frequencies, implications for autoimmunity" 230:– this means that they are able to directly kill virus-infected cells, as well as cancer cells. CD8+ T cells are also able to use small signalling proteins, known as 4830:

Penaloza-MacMaster P, Kamphorst AO, Wieland A, Araki K, Iyer SS, West EE, O'Mara L, Yang S, Konieczny BT, Sharpe AH, Freeman GJ, Rudensky AY, Ahmed R (August 2014).

1656:. Exhaustion can develop during chronic infections, sepsis and cancer. Exhausted T cells preserve their functional exhaustion even after repeated antigen exposure. 1285: 1261:

and ICOS, but these largely depend upon CD28 for their expression. The second signal licenses the T cell to respond to an antigen. Without it, the T cell becomes

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The first signal is provided by binding of the T cell receptor to its cognate peptide presented on MHCII on an APC. MHCII is restricted to so-called professional

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Sallusto F, Lenig D, Förster R, Lipp M, Lanzavecchia A (1999). "Two subsets of memory T lymphocytes with distinct homing potentials and effector functions".

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that activates the transcription of a pleiotropic set of genes, most notable, IL-2, a cytokine that promotes long-term proliferation of activated T cells.

386:, called negative selection. If both positive and negative selection are successful, the TCR becomes fully operational and the thymocyte becomes a T cell. 3856:

Jennifer Rolland and Robyn O'Hehir, "Turning off the T cells: Peptides for treatment of allergic Diseases," Today's life science publishing, 1999, Page 32

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cell depends on its subtype (such as T-helper1, T-helper2, T-helper17, regulatory T-cell), which is distinguished by the types of cytokines they secrete.

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Gassa A, Jian F, Kalkavan H, Duhan V, Honke N, Shaabani N, Friedrich SK, Dolff S, Wahlers T, Kribben A, Hardt C, Lang PA, Witzke O, Lang KS (2016).

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are able to distinguish invading cells from "self". This prevents immune cells from inappropriately reacting against one's own cells, known as an "

6247: 5840: 1375:. DAG activates PKC-θ, which then phosphorylates CARMA1, causing it to unfold and function as a scaffold. The cytosolic domains bind an adapter 415:

The process of positive selection takes 3 to 4 days and occurs in the thymic cortex. Double-positive thymocytes (CD4/CD8) migrate deep into the

5356:"CMV Primary Infection Is Associated With Donor-Specific T Cell Hyporesponsiveness and Fewer Late Acute Rejections After Liver Transplantation" 5884: 5830: 4246: 3927: 2481: 1135:, which are produced by virtually all living cells. The most common phosphoantigens from animal and human cells (including cancer cells) are 3438:

Serriari NE, Eoche M, Lamotte L, Lion J, Fumery M, Marcelo P, Chatelain D, Barre A, Nguyen-Khac E, Lantz O, Dupas JL, Treiner E (May 2014).

3042:"Invariant and noninvariant natural killer T cells exert opposite regulatory functions on the immune response during murine schistosomiasis" 4442:"Hepatitis B Virus-Specific CD8+ T Cells Maintain Functional Exhaustion after Antigen Reexposure in an Acute Activation Immune Environment" 3040:

Mallevaey T, Fontaine J, Breuilh L, Paget C, Castro-Keller A, Vendeville C, Capron M, Leite-de-Moraes M, Trottein F, Faveeuw C (May 2007).

5273:"Cytomegalovirus-Induced Expression of CD244 after Liver Transplantation Is Associated with CD8+ T Cell Hyporesponsiveness to Alloantigen" 2011:"Distinct phases in the positive selection of CD8+ T cells distinguished by intrathymic migration and T-cell receptor signaling patterns" 6103: 1477: 1214: 1045: 4632:

Okagawa T, Konnai S, Nishimori A, Maekawa N, Goto S, Ikebuchi R, Kohara J, Suzuki Y, Yamada S, Kato Y, Murata S, Ohashi K (June 2018).

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Milstein O, Hagin D, Lask A, Reich-Zeliger S, Shezen E, Ophir E, Eidelstein Y, Afik R, Antebi YE, Dustin ML, Reisner Y (January 2011).

1245:. The only co-stimulatory receptor expressed constitutively by naive T cells is CD28, so co-stimulation for these cells comes from the 6240: 1577: 4734:"Cell-intrinsic transforming growth factor-beta signaling mediates virus-specific CD8+ T cell deletion and viral persistence in vivo" 328:(DN1) cells. To become T cells, the thymocytes must undergo multiple DN stages as well as positive selection and negative selection. 2261: 1993: 1769: 461: 451:. The potentially autoimmune cells are removed by the following process of negative selection, which occurs in the thymic medulla. 877:

stands for terminally differentiated effector memory cells re-expressing CD45RA, which is a marker usually found on naive T cells.

6586: 6139: 1728: 1465: 1316: 1029: 424: 379: 140: 5730: 5683:"PD-1(hi)TIM-3(+) T cells associate with and predict leukemia relapse in AML patients post allogeneic stem cell transplantation" 5174:"Disappearance of T Cell-Mediated Rejection Despite Continued Antibody-Mediated Rejection in Late Kidney Transplant Recipients" 4832:"Interplay between regulatory T cells and PD-1 in modulating T cell exhaustion and viral control during chronic LCMV infection" 1682: 554:

Depiction of the various key subsets of CD4-positive T cells with corresponding associated cytokines and transcription factors.

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Godfrey DI, Uldrich AP, McCluskey J, Rossjohn J, Moody DB (November 2015). "The burgeoning family of unconventional T cells".

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Wu H, Arron JR (November 2003). "TRAF6, a molecular bridge spanning adaptive immunity, innate immunity and osteoimmunology".

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and in the peripheral circulation. (Note- CD44 expression is usually used to distinguish murine naive from memory T cells).

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and serves to prevent the formation of self-reactive T cells that are capable of inducing autoimmune diseases in the host.

6524: 6062: 1485: 839: 395: 382:(MHC) in a process known as positive selection. The thymocyte must also ensure that it does not react adversely to "self" 128: 3196:

Eckle SB, Corbett AJ, Keller AN, Chen Z, Godfrey DI, Liu L, Mak JY, Fairlie DP, Rossjohn J, McCluskey J (December 2015).

2153: 1776:. Bethesda, MD: National Institutes of Health, U.S. Department of Health and Human Services. 17 June 2001. Archived from 1493: 6184: 6154: 6134: 1685:

are also able to trigger exhaustion. Last known factors that can play a role in T cell exhaustion are regulatory cells.

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protein, (B7.1 and B7.2, respectively) on the APC. Other receptors are expressed upon activation of the T cell, such as

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A thymocyte's fate is determined during positive selection. Double-positive cells (CD4/CD8) that interact well with MHC

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and cytotoxic T cells, which leads to a larger immune response. The specific adaptive immune response regulated by the T

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of T cells and/or defects on function of individual T cells. Complete insufficiency of T cell function can result from

873:. These memory T cells lack lymph node-homing receptors and are thus found in the peripheral circulation and tissues. T 6172: 6167: 6007: 5455:"Immune inhibitory molecules LAG-3 and PD-1 synergistically regulate T-cell function to promote tumoral immune escape" 5223:"Exhaustive differentiation of alloreactive CD8+ T cells: critical for determination of graft acceptance or rejection" 1637: 1522: 1395: 1312: 1301: 1140: 782:

cells, CTLs, T-killer cells, killer T cells) destroy virus-infected cells and tumor cells, and are also implicated in

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Zelle-Rieser C, Thangavadivel S, Biedermann R, Brunner A, Stoitzner P, Willenbacher E, et al. (November 2016).

6410: 1554: 1391: 1331:. PLC-γ cleaves PI(4,5)P2 on the inner leaflet of the membrane to create the active intermediaries diacylglycerol ( 1210: 1116: 1091: 887:) occupy tissues (skin, lung, etc.) without recirculating. One cell surface marker that has been associated with T 5877: 1559: 1328: 1202: 1136: 1070:

metabolites to MAIT cells. After the presentation of foreign antigen by MR1, MAIT cells secrete pro-inflammatory

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Several other types of T cells have suppressive activity, but do not express FOXP3 constitutively. These include

923:. Their major role is to shut down T cell–mediated immunity toward the end of an immune reaction and to suppress 3757:

Shedlock DJ, Shen H (April 2003). "Requirement for CD4 T cell help in generating functional CD8 T cell memory".

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is needed to establish exhaustion. Another factor able to induce exhaustion are inhibitory receptors including

1120: 968: 278: 188: 169: 116: 104: 3810:"CD4+ T cells are required for the maintenance, not programming, of memory CD8+ T cells after acute infection" 5970: 4036: 3866:

Maverakis E, Kim K, Shimoda M, Gershwin M, Patel F, Wilken R, Raychaudhuri S, Ruhaak LR, Lebrilla CB (2015).

6590: 6348: 6211: 5757:"Control of Toxoplasma reactivation by rescue of dysfunctional CD8+ T-cell response via PD-1-PDL-1 blockade" 1666: 1406: 1230: 1190: 920: 790:

protein on their cell surface. Cytotoxic T cells recognize their targets by binding to short peptides (8-11

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mission to study how "deficiencies in the human immune system are affected by a microgravity environment".

767: 39: 6693: 6612: 6330: 6266: 6054: 4262: 2363:"T Helper (Th) Cell Profiles in Pregnancy and Recurrent Pregnancy Losses: Th1/Th2/Th9/Th17/Th22/Tfh Cells" 1500: 1336: 1079: 1021: 894: 289:. The HSC then differentiate into multipotent progenitors (MPP) which retain the potential to become both 4542:"Progressive loss of memory T cell potential and commitment to exhaustion during chronic viral infection" 1602: 1347:

is released from the membrane by PLC-γ and diffuses rapidly to activate calcium channel receptors on the

6559: 6415: 6393: 6093: 6070: 6046: 5555:"Cancer-associated fibroblasts induce antigen-specific deletion of CD8 T Cells to protect tumour cells" 1489: 1348: 1344: 1013: 1008: 286: 181: 1284:

proteins: CD3εγ and CD3εδ heterodimers and, most important, a CD3ζ homodimer, which has a total of six

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immune response and has a memory-like phenotype. Furthermore, MAIT cells are thought to play a role in

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At the DN2 stage (CD44CD25), cells upregulate the recombination genes RAG1 and RAG2 and re-arrange the

5851: 3658: 2205:"Neonatal and adult recent thymic emigrants produce IL-8 and express complement receptors CR1 and CR2" 121: 6688: 6576: 6509: 6420: 6344: 6117: 5934: 5870: 5768: 5566: 5405:"Recipient T Cell Exhaustion and Successful Adoptive Transfer of Haploidentical Natural Killer Cells" 4493:"CD4+ T cells are required to sustain CD8+ cytotoxic T-cell responses during chronic viral infection" 3766: 3715: 3612: 3500: 3305:"MR1-Restricted Mucosal-Associated Invariant T Cells and Their Activation during Infectious Diseases" 2907:"Modulation of autoimmune diseases by interleukin (IL)-17 producing regulatory T helper (Th17) cells" 2514: 2022: 1547: 1505: 1461: 1365: 1051: 1025: 947: 654:

Produce an inflammatory response, key for defense against intracellular bacteria, viruses and cancer.

465: 6232: 5610:

Conforti L (February 2012). "The ion channel network in T lymphocytes, a target for immunotherapy".

3489:"MR1 antigen presentation to mucosal-associated invariant T cells was highly conserved in evolution" 3356:"Mucosal-associated invariant T cells in autoimmunity, immune-mediated diseases and airways disease" 1441: 435:

molecules will eventually become CD4 "helper" cells, whereas thymocytes that interact well with MHC

6698: 6636: 6571: 6554: 6388: 6306: 6126: 5965: 3988:"CTLs respond with activation and granule secretion when serving as targets for T cell recognition" 1748: 1733: 1700: 1242: 1017: 924: 399: 210:

One of these functions is immune-mediated cell death, and it is carried out by two major subtypes:

3597: 6456: 6098: 6085: 5403:

Williams RL, Cooley S, Bachanova V, Blazar BR, Weisdorf DJ, Miller JS, Verneris MR (March 2018).

5385: 5253: 5105: 4881:"The late phase of sepsis is characterized by an increased microbiological burden and death rate" 4614: 4440:

Wang Q, Pan W, Liu Y, Luo J, Zhu D, Lu Y, Feng X, Yang X, Dittmer U, Lu M, Yang D, Liu J (2018).

3968: 3790: 3739: 3636: 3577: 3440:"Innate mucosal-associated invariant T (MAIT) cells are activated in inflammatory bowel diseases" 2989:

de Araújo ND, Gama FM, de Souza Barros M, Ribeiro TL, Alves FS, Xabregas LA, et al. (2021).

2971: 2887: 2639: 2587: 2538: 2184: 2152:

Hinterberger M, Aichinger M, Prazeres da Costa O, Voehringer D, Hoffmann R, Klein L (June 2010).

2134: 1352: 1108: 1103: 1087: 1083: 958: 4879:

Otto GP, Sossdorf M, Claus RA, Rödel J, Menge K, Reinhart K, Bauer M, Riedemann NC (July 2011).

1563: 2659:"Multiparameter flow cytometric analysis of CD4 and CD8 T cell subsets in young and old people" 2607:"Molecular signatures distinguish human central memory from effector memory CD8 T cell subsets" 1831:

T cells ... derive their from the organs in which they develop. T cells develop in the thymus

6504: 6270: 6149: 6030: 5949: 5929: 5826: 5796: 5712: 5663: 5627: 5592: 5535: 5484: 5434: 5377: 5335: 5294: 5245: 5203: 5154: 5097: 5062: 5013: 4964: 4912: 4861: 4812: 4763: 4714: 4665: 4606: 4571: 4522: 4473: 4422: 4373: 4324: 4242: 4236: 4194: 4145: 4093: 4017: 3960: 3923: 3897: 3839: 3782: 3731: 3688: 3628: 3569: 3528: 3469: 3420: 3385: 3336: 3280: 3229: 3178: 3129: 3071: 3022: 2963: 2928: 2879: 2838: 2788: 2739: 2690: 2631: 2579: 2530: 2487: 2477: 2446: 2394: 2343: 2294: 2257: 2234: 2176: 2126: 2085: 2068:

Starr TK, Jameson SC, Hogquist KA (2003-01-01). "Positive and negative selection of T cells".

2050: 1989: 1966: 1917: 1876: 1686: 1607: 1567: 1481: 1453: 1436: 916: 911: 578: 502: 249: 5504:"T cells in multiple myeloma display features of exhaustion and senescence at the tumor site" 4982:

Shindo Y, McDonough JS, Chang KC, Ramachandra M, Sasikumar PG, Hotchkiss RS (February 2017).

3684: 2081: 593:

glycoprotein on their surfaces. Helper T cells become activated when they are presented with

6683: 6624: 6564: 6536: 6531: 6499: 6486: 6476: 6022: 5998: 5786: 5776: 5702: 5694: 5655: 5619: 5582: 5574: 5525: 5515: 5474: 5466: 5424: 5416: 5367: 5325: 5284: 5237: 5222: 5193: 5185: 5144: 5136: 5089: 5052: 5044: 5003: 4995: 4954: 4946: 4902: 4892: 4851: 4843: 4802: 4794: 4753: 4745: 4704: 4696: 4655: 4645: 4598: 4561: 4553: 4512: 4504: 4463: 4453: 4412: 4404: 4363: 4355: 4314: 4304: 4184: 4176: 4135: 4127: 4083: 4073: 4007: 3999: 3952: 3887: 3879: 3829: 3821: 3774: 3723: 3680: 3620: 3559: 3518: 3508: 3459: 3451: 3412: 3375: 3367: 3326: 3316: 3270: 3260: 3219: 3209: 3198:"Recognition of Vitamin B Precursors and Byproducts by Mucosal Associated Invariant T Cells" 3168: 3160: 3119: 3109: 3061: 3053: 3012: 3002: 2955: 2918: 2869: 2828: 2820: 2778: 2770: 2729: 2721: 2680: 2670: 2621: 2569: 2522: 2469: 2436: 2428: 2384: 2374: 2333: 2325: 2286: 2224: 2216: 2168: 2116: 2077: 2040: 2030: 1956: 1948: 1907: 1866: 1856: 1743: 1713: 1372: 1281: 814: 783: 775: 762: 468:

positive (AIRE) to properly express self-antigens from all tissues of the body on their MHC

253: 211: 161: 1054:, effector-like qualities. In humans, MAIT cells are found in the blood, liver, lungs, and 6519: 6014: 1543: 1534: 1457: 1418: 1269: 1174: 1160: 1148: 1055: 972: 961: 364: 204: 177: 4342:

Blank CU, Haining WN, Held W, Hogan PG, Kallies A, Lugli E, et al. (November 2019).

4215: 2154:"Autonomous role of medullary thymic epithelial cells in central CD4(+) T cell tolerance" 1777: 5772: 5570: 5129:

Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences

4683:

Brooks DG, Trifilo MJ, Edelmann KH, Teyton L, McGavern DB, Oldstone MB (November 2006).

3770: 3719: 3616: 3504: 2518: 2026: 1937:"Impaired CD8 T cell memory and CD4 T cell primary responses in IL-7R alpha mutant mice" 6546: 6491: 6432: 6352: 6325: 5820: 5791: 5756: 5707: 5682: 5587: 5554: 5530: 5503: 5479: 5454: 5429: 5404: 5198: 5173: 5149: 5124: 5057: 5032: 5008: 4983: 4959: 4934: 4907: 4880: 4856: 4831: 4807: 4782: 4758: 4733: 4709: 4684: 4660: 4633: 4566: 4541: 4468: 4441: 4417: 4392: 4368: 4343: 4319: 4292: 4189: 4164: 4140: 4115: 4088: 4061: 4012: 3987: 3892: 3867: 3834: 3809: 3523: 3488: 3464: 3439: 3380: 3355: 3331: 3304: 3275: 3248: 3224: 3197: 3173: 3148: 3124: 3097: 3066: 3041: 3017: 2990: 2923: 2906: 2833: 2808: 2783: 2758: 2734: 2709: 2685: 2658: 2441: 2416: 2389: 2362: 2338: 2313: 2229: 2204: 2045: 2010: 1961: 1936: 1935:

Osborne LC, Dhanji S, Snow JW, Priatel JJ, Ma MC, Miners MJ, et al. (March 2007).

1871: 1844: 1678: 1469: 1201:. The signalling pathways downstream from co-stimulatory molecules usually engages the 1194: 1132: 477: 294: 57: 4517: 4492: 3487:

Huang S, Martin E, Kim S, Yu L, Soudais C, Fremont DH, Lantz O, Hansen TH (May 2009).

2121: 2105:"The MHC reactivity of the T cell repertoire prior to positive and negative selection" 2104: 1193:. Both are required for production of an effective immune response; in the absence of 550: 252:

are yet another distinct population of T cells that provide the critical mechanism of

51: 6677: 6514: 6403: 6221: 6203: 6041: 6003: 5924: 4508: 4408: 4116:"Quantitative challenges in understanding ligand discrimination by alphabeta T cells" 2290: 1633: 1511: 1222: 819: 808: 574: 558: 545: 493:

signal that leads to cell death. However, some of these cells are selected to become

336: 239: 215: 165: 80: 5257: 5109: 4618: 3972: 3794: 3581: 2975: 2891: 2643: 2591: 2188: 2138: 711:

Defense against helminths (parasitic worms) and cell-dependent allergic inflammation

281:(HSC) which reside in the bone marrow. In some cases, the origin might be the fetal 6481: 6466: 6461: 6398: 6296: 6036: 5939: 5389: 5031:

Patera AC, Drewry AM, Chang K, Beiter ER, Osborne D, Hotchkiss RS (December 2016).

3640: 2991:"Translating Unconventional T Cells and Their Roles in Leukemia Antitumor Immunity" 2542: 1399: 1254: 1028:. Unlike conventional T cells that recognize protein peptide antigens presented by 601: 501:, also known as recent thymic emigrants. This process is an important component of 498: 473: 448: 321: 290: 261: 257: 227: 75: 5681:

Kong Y, Zhang J, Claxton DF, Ehmann WC, Rybka WB, Zhu L, et al. (July 2015).

5470: 3743: 2468:. Advances in Experimental Medicine and Biology. Vol. 841. pp. 209–230. 673:

Immunologically important against extracellular pathogens, such as worm infections

5314:"IL-10 Induces T Cell Exhaustion During Transplantation of Virus Infected Hearts" 4749: 4309: 4131: 4003: 3164: 1912: 1895: 109: 6216: 5919: 5914: 5241: 3416: 2626: 2574: 2557: 2473: 1738: 1612: 1380: 1357: 1332: 1165: 1059: 795: 570: 298: 192: 173: 5761:

Proceedings of the National Academy of Sciences of the United States of America

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Williams MA, Bevan MJ (2007-01-01). "Effector and memory CTL differentiation".

3493:

Proceedings of the National Academy of Sciences of the United States of America

2857: 2824: 2015:

Proceedings of the National Academy of Sciences of the United States of America

1803: 771:

Superresolution image of a group of cytotoxic T cells surrounding a cancer cell

17: 6604: 6357: 6263: 5893: 5520: 4999: 4650: 4359: 4078: 3249:"Mucosal-associated invariant T-cells: new players in anti-bacterial immunity" 2432: 2220: 2009:

Ross JO, Melichar HJ, Au-Yeung BB, Herzmark P, Weiss A, Robey EA (June 2014).

1649: 1324: 1308:, which allows the aggregation of signalling complexes around these proteins. 1128: 1067: 1063: 980: 866: 851: 843: 791: 582: 5289: 5272: 5048: 4458: 4180: 3321: 3265: 3114: 2774: 2379: 846:(CD62L). Central memory T cells also have intermediate to high expression of 747:

Pathogenesis of allergic airway diseases and predominantly anti-inflammatory

6662: 6367: 6189: 6144: 5992: 5781: 4935:"Immunosuppression in patients who die of sepsis and multiple organ failure" 4220: 3868:"Glycans in the immune system and The Altered Glycan Theory of Autoimmunity" 3778: 3513: 3214: 3098:"The Role of Mucosal Associated Invariant T Cells in Antimicrobial Immunity" 2035: 1297: 1173:

Activation of CD4 T cells occurs through the simultaneous engagement of the

700: 490: 302: 5800: 5716: 5667: 5631: 5596: 5539: 5488: 5438: 5381: 5339: 5298: 5249: 5207: 5189: 5158: 5140: 5101: 5066: 5017: 4968: 4950: 4916: 4865: 4816: 4767: 4718: 4669: 4610: 4575: 4477: 4426: 4377: 4328: 4198: 4149: 4097: 4021: 3964: 3901: 3843: 3786: 3735: 3692: 3632: 3573: 3532: 3473: 3424: 3389: 3340: 3284: 3233: 3182: 3149:"Mucosal associated invariant T cells and the immune response to infection" 3133: 3075: 3026: 3007: 2967: 2932: 2883: 2842: 2792: 2743: 2694: 2657:

Koch S, Larbi A, Derhovanessian E, Özcelik D, Naumova E, Pawelec G (2008).

2635: 2558:"Loss of CD45R and gain of UCHL1 reactivity is a feature of primed T cells" 2534: 2491: 2450: 2398: 2347: 2298: 2238: 2180: 2089: 2054: 1970: 1921: 1880: 4526: 2675: 2583: 2314:"APC-derived cytokines and T cell polarization in autoimmune inflammation" 2130: 1861: 331:

Double negative thymocytes can be identified by the surface expression of

6652: 6437: 6425: 6383: 6337: 6301: 5958: 5909: 4847: 4557: 3564: 3547: 3057: 1952: 1517: 1445: 1340: 1238: 1071: 976: 638: 609: 371: 231: 61: 5698: 5221:

Steger U, Denecke C, Sawitzki B, Karim M, Jones ND, Wood KJ (May 2008).

4293:"Immunological exhaustion: How to make a disparate concept operational?" 3727: 3624: 218:

T cells. (These are named for the presence of the cell surface proteins

6657: 6471: 6320: 6291: 6177: 3956: 1186: 1124: 643: 597: 594: 420: 383: 5372: 5355: 5330: 5313: 4798: 3455: 3371: 2725: 1032:(MHC) molecules, NKT cells recognize glycolipid antigens presented by 146: 6629: 6362: 6313: 5944: 5901: 5125:"The role of peripheral T-cell deletion in transplantation tolerance" 2329: 1670: 1539: 1262: 1198: 1144: 1112: 566: 416: 200: 196: 5731:"U.S. FDA Approved Immune-Checkpoint Inhibitors and Immunotherapies" 5553:

Lakins MA, Ghorani E, Munir H, Martins CP, Shields JD (March 2018).

4897: 4602: 2959: 2905:

Singh B, Schwartz JA, Sandrock C, Bellemore SM, Nikoopour E (2013).

2874: 2605:

Willinger T, Freeman T, Hasegawa H, McMichael AJ, Callan MF (2005).

2172: 4700: 4540:

Angelosanto JM, Blackburn SD, Crawford A, Wherry EJ (August 2012).

3825: 1821:

Alberts B, Johnson A, Lewis J, Raff M, Roberts K, Walter P (2002).

1802:

Alberts B, Johnson A, Lewis J, Raff M, Roberts K, Walter P (2002).

308:

The earliest cells which arrived in the thymus are commonly termed

4685:"Interleukin-10 determines viral clearance or persistence in vivo" 3654: 2858:"Regulatory T cells: recommendations to simplify the nomenclature" 2526: 1440: 1376: 1293: 1218: 1182: 1164: 1075: 957:

gene can prevent regulatory T cell development, causing the fatal

950: 766: 649: 549: 282: 92: 2556:

Akbar AN, Terry L, Timms A, Beverley PC, Janossy G (April 1988).

1896:"One Niche to Rule Both Maintenance and Loss of Stemness in HSCs" 1143:(DMPP). Many microbes produce the active compound hydroxy-DMAPP ( 199:

gland to develop (or mature). T cells derive their name from the

1674: 1645: 1641: 1361: 1320: 1258: 1250: 1246: 1206: 1185:) on the T cell by the major histocompatibility complex (MHCII) 1178: 1033: 870: 847: 824: 681: 494: 344: 6236: 5866: 2464:

Jia L, Wu C (2014). "The Biology and Functions of Th22 Cells".

1476:. Causes of partial insufficiencies of T cell function include 813:

Antigen-naive T cells expand and differentiate into memory and

5862: 5822:

Immunobiology 5 : the immune system in health and disease

1587: 1289: 927:

that escaped the process of negative selection in the thymus.

787: 662: 590: 348: 340: 332: 317: 313: 223: 219: 5735:

Medical Writer Agency | 香港醫學作家 | MediPR | MediPaper Hong Kong

4732:

Tinoco R, Alcalde V, Yang Y, Sauer K, Zuniga EI (July 2009).

2361:

Wang W, Sung N, Gilman-Sachs A, Kwak-Kim J (18 August 2020).

1288:

motifs. The ITAM motifs on the CD3ζ can be phosphorylated by

565:

cells) assist other lymphocytes, including the maturation of

3598:"MR1 presents microbial vitamin B metabolites to MAIT cells" 1315:

recruits SLP-76 to the membrane, where it can then bring in

786:

rejection. These cells are defined by the expression of the

4393:"T-cell exhaustion: characteristics, causes and conversion" 1648:

and inhibitory receptors combined with lower expression of

447:

This process does not filter for thymocytes that may cause

5819:

Janeway Jr CA, Travers P, Walport M, Shlomchik MJ (2001).

4268:. The Leukemia & Lymphoma Society. May 2006. p. 2 1058:, defending against microbial activity and infection. The 953:

which can be used to identify the cells. Mutations of the

484:(APCs), allowing for presentation of self-antigens on MHC 4037:"SpaceX ready for CRS-3 Dragon launch and new milestones" 3096:

Napier RJ, Adams EJ, Gold MC, Lewinsohn DM (2015-07-06).

1499:

The main pathogens of concern in T cell deficiencies are

1488:(CBSs), and B cell and T cell combined disorders such as 946:

respectively. Both subsets require the expression of the

3548:"Bacteria, mucosal-associated invariant T cells and MR1" 1525:

are also more common and severe in T cell deficiencies.

608:(APCs). Once activated, they divide rapidly and secrete 351:

is expressed. Expression of both CD4 and CD8 makes them

1094:, although definitive evidence is yet to be published. 4781:

Veiga-Parga T, Sehrawat S, Rouse BT (September 2013).

4491:

Matloubian M, Concepcion RJ, Ahmed R (December 1994).

4165:"An induced rebinding model of antigen discrimination" 865:

cells) express CD45RO but lack expression of CCR7 and

5848:

National Institute of Allergy and Infectious Diseases

1066:, is responsible for presenting bacterially-produced 850:. This memory subpopulation is commonly found in the 692:

Defense against gut pathogens and at mucosal barriers

497:

cells. The remaining cells exit the thymus as mature

273:

Origin, early development and migration to the thymus

226:.) CD8+ T cells, also known as "killer T cells", are 4230: 4228: 3913: 3911: 1364:, which then translocates to the nucleus. NFAT is a 1050:

Mucosal associated invariant T (MAIT) cells display

869:. They also have intermediate to high expression of 6645: 6603: 6545: 6446: 6376: 6284: 6277: 6202: 6125: 6116: 6084: 5979: 5900: 5755:Bhadra R, Gigley JP, Weiss LM, Khan IA (May 2011). 4783:"Role of regulatory T cells during virus infection" 1988:(8th ed.). Garland Science. pp. 301–305. 1280:) genes. The other proteins in the complex are the 127: 115: 103: 91: 86: 74: 69: 32: 4634:"+ T cells during bovine leukemia virus infection" 4291:Kaminski H, Lemoine M, Pradeu T (September 2021). 4235:Jones J, Bannister BA, Gillespie SH, eds. (2006). 4060:Belikov AV, Schraven B, Simeoni L (October 2015). 3247:Ussher JE, Klenerman P, Willberg CB (2014-10-08). 2410: 2408: 4928: 4926: 4109: 4107: 604:molecules, which are expressed on the surface of 5123:Wells AD, Li XC, Strom TB, Turka LA (May 2001). 4984:"Anti-PD-L1 peptide improves survival in sepsis" 4114:Feinerman O, Germain RN, Altan-Bonnet G (2008). 3808:Sun JC, Williams MA, Bevan MJ (September 2004). 2466:T Helper Cell Differentiation and Their Function 4210: 4208: 1843:Luckheeram RV, Zhou R, Verma AD, Xia B (2012). 1829:(4th ed.). Garland Science. p. 1367. 1546:, and accounts for perhaps one in ten cases of 1296:. Lck and/or ZAP-70 can also phosphorylate the 64:(center), and a T lymphocyte (right); colorized 3303:Howson LJ, Salio M, Cerundolo V (2015-06-16). 2759:"Alternative memory in the CD8 T cell lineage" 2256:(8th ed.). Garland Science. p. 297. 1797: 1795: 1197:, T cell receptor signalling alone results in 750:Crohn's Disease, Rheumatoid Arthritis, Tumors 355:, and matures into either CD4+ or CD8+ cells. 6248: 5878: 5178:Journal of the American Society of Nephrology 8: 4589:Wherry EJ (June 2011). "T cell exhaustion". 4286: 4284: 4282: 1845:"CD4⁺T cells: differentiation and functions" 1677:(LAG3). Soluble molecules such as cytokines 5825:(5th ed.). New York: Garland Science. 5409:Biology of Blood and Marrow Transplantation 2103:Zerrahn J, Held W, Raulet DH (March 1997). 1601:It has been suggested that this section be 343:. Still during the double negative stages, 6281: 6255: 6241: 6233: 6122: 5985: 5885: 5871: 5863: 2415:Saravia J, Chapman NM, Chi H (July 2019). 1823:"Helper t Cells and Lymphocyte Activation" 1804:"Helper T Cells and Lymphocyte Activation" 1480:(AIDS), and hereditary conditions such as 172:. T cells can be distinguished from other 50: 38: 5790: 5780: 5706: 5586: 5529: 5519: 5478: 5428: 5371: 5329: 5288: 5197: 5148: 5056: 5007: 4958: 4906: 4896: 4855: 4806: 4757: 4708: 4659: 4649: 4565: 4516: 4467: 4457: 4416: 4367: 4318: 4308: 4188: 4139: 4087: 4077: 4011: 3918:Tatham P, Gomperts BD, Kramer IM (2003). 3891: 3833: 3563: 3522: 3512: 3463: 3379: 3330: 3320: 3274: 3264: 3223: 3213: 3172: 3123: 3113: 3065: 3016: 3006: 2922: 2873: 2832: 2782: 2733: 2684: 2674: 2625: 2573: 2440: 2388: 2378: 2337: 2228: 2120: 2044: 2034: 1960: 1911: 1870: 1860: 1550:. The main forms of T cell lymphoma are: 1300:on many other molecules, not least CD28, 1217:that are essential for the activation of 1151:, which upregulate endogenous IPP/DMAPP. 195:. Developing T cells then migrate to the 3685:10.1146/annurev.immunol.25.022106.141548 2757:Lee YJ, Jameson SC, Hogquist KA (2011). 2082:10.1146/annurev.immunol.21.120601.141107 1673:, T cell membrane protein-3 (TIM3), and 1253:proteins, which together constitute the 1161:T-cell receptor § Signaling pathway 1020:of the innate immune system) bridge the 891:is the intern αeβ7, also known as CD103. 614: 3659:"Understanding the Immune System (pdf)" 1849:Clinical & Developmental Immunology 1761: 423:. These self-antigens are expressed by 238:) cells function by further activating 4391:Yi JS, Cox MA, Zajac AJ (April 2010). 4238:Infection: Microbiology and Management 3922:. Amsterdam: Elsevier Academic Press. 3298: 3296: 3294: 3091: 3089: 3087: 3085: 1394:(TCAS) experiment was launched to the 1209:at the plasma membrane and recruiting 144: 29: 27:White blood cells of the immune system 4062:"T cells and reactive oxygen species" 3147:Gold MC, Lewinsohn DM (August 2011). 1605:out into another article titled 1016:(NKT cells – not to be confused with 531:gene or protein expression patterns. 419:, where they are presented with self- 277:All T cells originate from c-kitSca1 7: 5508:Journal of Hematology & Oncology 5318:Cellular Physiology and Biochemistry 4836:The Journal of Experimental Medicine 3546:Chua WJ, Hansen TH (November 2010). 3444:Clinical and Experimental Immunology 2708:Shin H, Iwasaki A (September 2013). 1941:The Journal of Experimental Medicine 1675:lymphocyte activation gene 3 protein 1213:containing signaling molecules like 1189:and co-stimulatory molecules on the 1177:and a co-stimulatory molecule (like 1040:Mucosal associated invariant T cells 695:MS, Rheumatoid Arthritis, Psoriasis 6104:Mucosal associated invariant T cell 5360:American Journal of Transplantation 4163:Dushek O, van der Merwe PA (2014). 3202:The Journal of Biological Chemistry 2421:Cellular & Molecular Immunology 1660:During chronic infection and sepsis 1478:acquired immune deficiency syndrome 1046:Mucosal associated invariant T cell 919:are crucial for the maintenance of 733:Asthma and other allergic diseases 676:Asthma and other allergic diseases 1578:Angioimmunoblastic T cell lymphoma 1405:T cell activation is modulated by 1360:. Calcineurin, in turn, activates 305:, the immature stage of a T cell. 160:are one of the important types of 56:Scanning electron micrograph of a 25: 1335:), inositol-1,4,5-trisphosphate ( 934:cells have been described—FOXP3 T 462:medullary thymic epithelial cells 6140:Lymphokine-activated killer cell 5850:. September 2003. Archived from 4988:The Journal of Surgical Research 4509:10.1128/JVI.68.12.8056-8063.1994 4409:10.1111/j.1365-2567.2010.03255.x 4241:. Wiley-Blackwell. p. 435. 2710:"Tissue-resident memory T cells" 2291:10.1146/annurev.immunol.18.1.529 1810:(4th ed.). Garland Science. 1729:Chimeric antigen receptor T cell 1592: 1466:severe combined immunodeficiency 1030:major histocompatibility complex 585:. These cells are also known as 425:thymic cortical epithelial cells 380:major histocompatibility complex 141:Anatomical terms of microanatomy 2417:"Helper T cell differentiation" 1667:programmed cell death protein 1 1351:, which induces the release of 1131:precursors, collectively named 730:Help B cells produce antibodies 301:. Henceforth they are known as 168:and play a central role in the 6582:Immunoglobulin class switching 4344:"Defining 'T cell exhaustion'" 2995:Journal of Immunology Research 1573:Anaplastic large cell lymphoma 1486:chromosomal breakage syndromes 983:have been added to this list. 881:Tissue-resident memory T cells 312:, as they express neither the 1: 5471:10.1158/0008-5472.CAN-11-1620 4066:Journal of Biomedical Science 2122:10.1016/S0092-8674(00)81905-4 1827:Molecular Biology of the Cell 1808:Molecular Biology of the Cell 1770:"5. Hematopoietic Stem Cells" 840:C-C chemokine receptor type 7 535:Conventional adaptive T cells 6185:Type 3 innate lymphoid cells 6173:Type 2 innate lymphoid cells 6168:Type 1 innate lymphoid cells 6155:Uterine natural killer cells 6135:Cytokine-induced killer cell 5037:Journal of Leukocyte Biology 4750:10.1016/j.immuni.2009.06.015 4310:10.1371/journal.ppat.1009892 4132:10.1016/j.molimm.2007.03.028 4004:10.1182/blood-2010-05-283770 3165:10.1016/j.micinf.2011.03.007 2312:Gutcher I, Becher B (2007). 1913:10.1016/j.immuni.2016.12.003 1371:PLC-γ can also initiate the 5242:10.1097/TP.0b013e31816dd64a 3673:Annual Review of Immunology 3552:Immunology and Cell Biology 3417:10.1016/j.imlet.2017.01.009 2627:10.4049/jimmunol.175.9.5895 2575:10.4049/jimmunol.140.7.2171 2474:10.1007/978-94-017-9487-9_8 2070:Annual Review of Immunology 1396:International Space Station 1141:dimethylallyl pyrophosphate 1117:intraepithelial lymphocytes 794:in length) associated with 616:CD4+ Helper T cell subsets 6715: 6411:Polyclonal B cell response 5660:10.1016/j.clim.2018.02.009 5624:10.1016/j.clim.2011.11.009 5579:10.1038/s41467-018-03347-0 5421:10.1016/j.bbmt.2017.11.022 5094:10.1016/j.clim.2018.04.010 4348:Nature Reviews. Immunology 3884:10.1016/j.jaut.2014.12.002 2825:10.1016/j.jaut.2016.11.001 1711: 1560:Cutaneous T cell lymphomas 1555:Extranodal T cell lymphoma 1532: 1434: 1392:T-Cell Activation in Space 1158: 1101: 1092:inflammatory bowel disease 1043: 1006: 930:Two major classes of CD4 T 909: 857:Effector memory T cells (T 806: 760: 543: 362: 6163: 5988: 5521:10.1186/s13045-016-0345-3 5000:10.1016/j.jss.2016.08.099 4651:10.1186/s13567-018-0543-9 4360:10.1038/s41577-019-0221-9 4079:10.1186/s12929-015-0194-3 2433:10.1038/s41423-019-0220-6 2221:10.1172/jci.insight.93739 1894:Kondo M (December 2016). 1474:cartilage–hair hypoplasia 1137:isopentenyl pyrophosphate 1115:, within a population of 834:Central memory T cells (T 472:peptides. Some mTECs are 279:haematopoietic stem cells 139: 49: 37: 5290:10.4049/jimmunol.1500440 5049:10.1189/jlb.4hi0616-255r 4459:10.3389/fimmu.2018.00219 4181:10.1016/j.it.2014.02.002 3322:10.3389/fimmu.2015.00303 3266:10.3389/fimmu.2014.00450 3115:10.3389/fimmu.2015.00344 2775:10.1016/j.it.2010.12.004 2380:10.3389/fimmu.2020.02025 2252:Murphy, Kenneth (2011). 1984:Murphy, Kenneth (2011). 1494:Wiskott–Aldrich syndrome 1231:antigen-presenting cells 830:Memory T cell subtypes: 627:Key Transcription Factor 606:antigen-presenting cells 482:antigen presenting cells 189:hematopoietic stem cells 170:adaptive immune response 6212:Hematopoietic stem cell 5971:Lymphoplasmacytoid cell 5782:10.1073/pnas.1015298108 4035:Graham W (2014-04-14). 3779:10.1126/science.1082305 3514:10.1073/pnas.0903196106 3309:Frontiers in Immunology 3253:Frontiers in Immunology 3215:10.1074/jbc.R115.685990 3102:Frontiers in Immunology 2813:Journal of Autoimmunity 2367:Frontiers in Immunology 2254:Janeway's Immunobiology 2036:10.1073/pnas.1408482111 1986:Janeway's Immunobiology 1501:intracellular pathogens 1407:reactive oxygen species 921:immunological tolerance 906:Regulatory CD4+ T cells 838:cells) express CD45RO, 509:TCR development summary 480:; this makes them AIRE 464:(mTECs). mTECs must be 6525:Tolerance in pregnancy 6267:adaptive immune system 5190:10.1681/ASN.2014060588 5141:10.1098/rstb.2001.0845 4951:10.1001/jama.2011.1829 3153:Microbes and Infection 3046:Infection and Immunity 1694:During transplantation 1449: 1413:Antigen discrimination 1170: 1022:adaptive immune system 1014:Natural killer T cells 996:unconventional T cells 895:Virtual memory T cells 772: 757:Cytotoxic CD8+ T cells 630:Role in immune defense 555: 478:thymic dendritic cells 187:T cells are born from 6560:Somatic hypermutation 6394:Polyclonal antibodies 6389:Monoclonal antibodies 6118:Innate lymphoid cells 6094:Natural killer T cell 5559:Nature Communications 5277:Journal of Immunology 4787:Immunological Reviews 3354:Hinks TS (May 2016). 2714:Immunological Reviews 2676:10.1186/1742-4933-5-6 2663:Immunity & Ageing 2614:Journal of Immunology 1774:Stem Cell Information 1542:of T cells is termed 1533:Further information: 1490:ataxia-telangiectasia 1462:hereditary conditions 1444: 1426:Clinical significance 1168: 1139:(IPP) and its isomer 1009:Natural killer T cell 1003:Natural killer T cell 770: 686:IL-17F, IL-17A, IL-22 553: 390:TCR β-chain selection 347:expression stops and 324:c-kit and are termed 287:embryonic development 176:by the presence of a 6577:Junctional diversity 6345:Antigen presentation 5687:Blood Cancer Journal 4848:10.1084/jem.20132577 4558:10.1128/JVI.00889-12 3565:10.1038/icb.2010.104 3058:10.1128/IAI.01178-06 3008:10.1155/2021/6633824 2763:Trends in Immunology 1953:10.1084/jem.20061871 1548:non-Hodgkin lymphoma 1506:Herpes simplex virus 1390:In spring 2014, the 1366:transcription factor 1292:and in turn recruit 1149:aminobisphosphonates 1026:innate immune system 1018:natural killer cells 948:transcription factor 925:autoreactive T cells 657:MS, Type 1 diabetes 589:as they express the 577:, and activation of 466:Autoimmune regulator 6572:V(D)J recombination 6555:Affinity maturation 6307:Antigenic variation 6086:Innate-like T cells 5966:Transitional B cell 5841:"The Immune System" 5773:2011PNAS..108.9196B 5699:10.1038/bcj.2015.58 5648:Clinical Immunology 5612:Clinical Immunology 5571:2018NatCo...9..948L 5082:Clinical Immunology 4638:Veterinary Research 4546:Journal of Virology 4497:Journal of Virology 4041:NASAspaceflight.com 3920:Signal transduction 3771:2003Sci...300..337S 3728:10.1038/nature01441 3720:2003Natur.421..852J 3625:10.1038/nature11605 3617:2012Natur.491..717K 3505:2009PNAS..106.8290H 2519:1999Natur.401..708S 2027:2014PNAS..111E2550R 2021:(25): E2550–E2558. 1862:10.1155/2012/925135 1749:Parafollicular cell 1734:Gut-specific homing 1243:heat shock proteins 1205:pathway generating 1109:Gamma delta T cells 1098:Gamma delta T cells 1084:autoimmune diseases 1074:and are capable of 992:Innate-like T cells 987:Innate-like T cells 714:Multiple Sclerosis 617: 540:Helper CD4+ T cells 400:V-D-J recombination 326:double-negative one 44:Animation of T cell 3957:10.1002/bies.10352 3405:Immunology Letters 2911:Indian J. Med. Res 2279:Annu. Rev. Immunol 1780:on 29 October 2016 1751:also called C cell 1450: 1356:can then activate 1171: 1104:Gamma delta T cell 1088:multiple sclerosis 959:autoimmune disease 917:Regulatory T cells 773: 624:Cytokines Produced 615: 556: 455:Negative selection 411:Positive selection 250:Regulatory T cells 122:H2.00.04.1.02007 6671: 6670: 6599: 6598: 6349:professional APCs 6230: 6229: 6198: 6197: 6112: 6111: 5832:978-0-8153-3642-6 5767:(22): 9196–9201. 5373:10.1111/ajt.13288 5331:10.1159/000443067 4799:10.1111/imr.12085 4591:Nature Immunology 4248:978-1-4051-2665-6 3929:978-0-12-289632-3 3814:Nature Immunology 3657:resource booklet 3456:10.1111/cei.12277 3372:10.1111/imm.12582 2954:(11): 1114–1123. 2948:Nature Immunology 2726:10.1111/imr.12087 2513:(6754): 708–712. 2483:978-94-017-9486-2 2161:Nature Immunology 1625: 1624: 1620: 1608:T cell exhaustion 1568:Mycosis fungoides 1523:fungal infections 1482:DiGeorge syndrome 1454:T cell deficiency 1437:T cell deficiency 938:cells and FOXP3 T 912:Regulatory T cell 776:Cytotoxic T cells 754: 753: 667:IL-4, IL-5, IL-13 633:Related diseases 579:cytotoxic T cells 503:central tolerance 398:locus, combining 162:white blood cells 155: 154: 150: 16:(Redirected from 6706: 6565:Clonal selection 6537:Immune privilege 6532:Immunodeficiency 6487:Cross-reactivity 6477:Hypersensitivity 6282: 6257: 6250: 6243: 6234: 6150:Adaptive NK cell 6123: 5986: 5887: 5880: 5873: 5864: 5858: 5857:on 25 June 2009. 5856: 5845: 5836: 5805: 5804: 5794: 5784: 5752: 5746: 5745: 5743: 5742: 5727: 5721: 5720: 5710: 5678: 5672: 5671: 5642: 5636: 5635: 5607: 5601: 5600: 5590: 5550: 5544: 5543: 5533: 5523: 5499: 5493: 5492: 5482: 5449: 5443: 5442: 5432: 5400: 5394: 5393: 5375: 5350: 5344: 5343: 5333: 5309: 5303: 5302: 5292: 5268: 5262: 5261: 5227: 5218: 5212: 5211: 5201: 5169: 5163: 5162: 5152: 5135:(1409): 617–23. 5120: 5114: 5113: 5077: 5071: 5070: 5060: 5043:(6): 1239–1254. 5028: 5022: 5021: 5011: 4979: 4973: 4972: 4962: 4945:(23): 2594–605. 4930: 4921: 4920: 4910: 4900: 4876: 4870: 4869: 4859: 4827: 4821: 4820: 4810: 4778: 4772: 4771: 4761: 4729: 4723: 4722: 4712: 4680: 4674: 4673: 4663: 4653: 4629: 4623: 4622: 4586: 4580: 4579: 4569: 4537: 4531: 4530: 4520: 4488: 4482: 4481: 4471: 4461: 4437: 4431: 4430: 4420: 4388: 4382: 4381: 4371: 4339: 4333: 4332: 4322: 4312: 4288: 4277: 4276: 4274: 4273: 4267: 4259: 4253: 4252: 4232: 4223: 4216:T-Cell Disorders 4212: 4203: 4202: 4192: 4160: 4154: 4153: 4143: 4111: 4102: 4101: 4091: 4081: 4057: 4051: 4050: 4048: 4047: 4032: 4026: 4025: 4015: 3983: 3977: 3976: 3951:(11): 1096–105. 3940: 3934: 3933: 3915: 3906: 3905: 3895: 3863: 3857: 3854: 3848: 3847: 3837: 3805: 3799: 3798: 3754: 3748: 3747: 3703: 3697: 3696: 3668: 3662: 3651: 3645: 3644: 3611:(7426): 717–23. 3602: 3592: 3586: 3585: 3567: 3543: 3537: 3536: 3526: 3516: 3484: 3478: 3477: 3467: 3435: 3429: 3428: 3400: 3394: 3393: 3383: 3351: 3345: 3344: 3334: 3324: 3300: 3289: 3288: 3278: 3268: 3244: 3238: 3237: 3227: 3217: 3208:(51): 30204–11. 3193: 3187: 3186: 3176: 3144: 3138: 3137: 3127: 3117: 3093: 3080: 3079: 3069: 3037: 3031: 3030: 3020: 3010: 2986: 2980: 2979: 2943: 2937: 2936: 2926: 2902: 2896: 2895: 2877: 2853: 2847: 2846: 2836: 2803: 2797: 2796: 2786: 2754: 2748: 2747: 2737: 2705: 2699: 2698: 2688: 2678: 2654: 2648: 2647: 2629: 2611: 2602: 2596: 2595: 2577: 2553: 2547: 2546: 2502: 2496: 2495: 2461: 2455: 2454: 2444: 2412: 2403: 2402: 2392: 2382: 2358: 2352: 2351: 2341: 2330:10.1172/JCI31720 2309: 2303: 2302: 2274: 2268: 2267: 2249: 2243: 2242: 2232: 2199: 2193: 2192: 2158: 2149: 2143: 2142: 2124: 2100: 2094: 2093: 2065: 2059: 2058: 2048: 2038: 2006: 2000: 1999: 1981: 1975: 1974: 1964: 1932: 1926: 1925: 1915: 1906:(6): 1177–1179. 1891: 1885: 1884: 1874: 1864: 1840: 1834: 1833: 1818: 1812: 1811: 1799: 1790: 1789: 1787: 1785: 1766: 1744:Immunosenescence 1714:Immunosenescence 1616: 1596: 1595: 1588: 1448:-infected T cell 1327:and potentially 1090:, arthritis and 815:effector T cells 763:Cytotoxic T cell 618: 214:(cytotoxic) and 147:edit on Wikidata 54: 42: 30: 21: 6714: 6713: 6709: 6708: 6707: 6705: 6704: 6703: 6674: 6673: 6672: 6667: 6641: 6595: 6541: 6520:Clonal deletion 6448: 6442: 6372: 6273: 6261: 6231: 6226: 6194: 6159: 6108: 6080: 6074: 6066: 6058: 6050: 6026: 6018: 6011: 5975: 5953: 5896: 5891: 5861: 5854: 5843: 5839: 5833: 5818: 5814: 5812:Further reading 5809: 5808: 5754: 5753: 5749: 5740: 5738: 5729: 5728: 5724: 5680: 5679: 5675: 5644: 5643: 5639: 5609: 5608: 5604: 5552: 5551: 5547: 5501: 5500: 5496: 5459:Cancer Research 5451: 5450: 5446: 5402: 5401: 5397: 5352: 5351: 5347: 5311: 5310: 5306: 5270: 5269: 5265: 5230:Transplantation 5225: 5220: 5219: 5215: 5171: 5170: 5166: 5122: 5121: 5117: 5079: 5078: 5074: 5030: 5029: 5025: 4981: 4980: 4976: 4932: 4931: 4924: 4898:10.1186/cc10332 4878: 4877: 4873: 4829: 4828: 4824: 4780: 4779: 4775: 4731: 4730: 4726: 4689:Nature Medicine 4682: 4681: 4677: 4631: 4630: 4626: 4603:10.1038/ni.2035 4588: 4587: 4583: 4552:(15): 8161–70. 4539: 4538: 4534: 4503:(12): 8056–63. 4490: 4489: 4485: 4439: 4438: 4434: 4390: 4389: 4385: 4354:(11): 665–674. 4341: 4340: 4336: 4303:(9): e1009892. 4290: 4289: 4280: 4271: 4269: 4265: 4263:"The Lymphomas" 4261: 4260: 4256: 4249: 4234: 4233: 4226: 4213: 4206: 4162: 4161: 4157: 4113: 4112: 4105: 4059: 4058: 4054: 4045: 4043: 4034: 4033: 4029: 3985: 3984: 3980: 3942: 3941: 3937: 3930: 3917: 3916: 3909: 3865: 3864: 3860: 3855: 3851: 3807: 3806: 3802: 3765:(5617): 337–9. 3756: 3755: 3751: 3714:(6925): 852–6. 3705: 3704: 3700: 3670: 3669: 3665: 3652: 3648: 3600: 3594: 3593: 3589: 3545: 3544: 3540: 3486: 3485: 3481: 3437: 3436: 3432: 3402: 3401: 3397: 3353: 3352: 3348: 3302: 3301: 3292: 3246: 3245: 3241: 3195: 3194: 3190: 3146: 3145: 3141: 3095: 3094: 3083: 3039: 3038: 3034: 2988: 2987: 2983: 2960:10.1038/ni.3298 2945: 2944: 2940: 2904: 2903: 2899: 2875:10.1038/ni.2554 2855: 2854: 2850: 2805: 2804: 2800: 2756: 2755: 2751: 2707: 2706: 2702: 2656: 2655: 2651: 2620:(9): 5895–903. 2609: 2604: 2603: 2599: 2555: 2554: 2550: 2504: 2503: 2499: 2484: 2463: 2462: 2458: 2414: 2413: 2406: 2360: 2359: 2355: 2318:J. Clin. Invest 2311: 2310: 2306: 2276: 2275: 2271: 2264: 2251: 2250: 2246: 2201: 2200: 2196: 2173:10.1038/ni.1874 2156: 2151: 2150: 2146: 2102: 2101: 2097: 2067: 2066: 2062: 2008: 2007: 2003: 1996: 1983: 1982: 1978: 1934: 1933: 1929: 1893: 1892: 1888: 1842: 1841: 1837: 1820: 1819: 1815: 1801: 1800: 1793: 1783: 1781: 1768: 1767: 1763: 1758: 1725: 1716: 1710: 1696: 1662: 1621: 1597: 1593: 1586: 1564:Sézary syndrome 1544:T-cell lymphoma 1537: 1535:T-cell lymphoma 1531: 1458:lymphocytopenia 1439: 1433: 1428: 1415: 1311:Phosphorylated 1270:T cell receptor 1221:, and eventual 1175:T-cell receptor 1163: 1157: 1133:phosphoantigens 1106: 1100: 1062:-like protein, 1048: 1042: 1011: 1005: 989: 941: 937: 933: 914: 908: 900: 890: 886: 876: 864: 860: 837: 811: 805: 781: 765: 759: 564: 548: 542: 537: 528: 526:Types of T cell 519: 511: 460:MHC complex of 457: 442:single positive 413: 405:double-positive 392: 367: 365:T-cell receptor 361: 359:TCR development 353:double positive 310:double-negative 275: 270: 245: 237: 205:immune response 191:, found in the 180:(TCR) on their 178:T-cell receptor 151: 65: 45: 28: 23: 22: 18:Effector T cell 15: 12: 11: 5: 6712: 6710: 6702: 6701: 6696: 6691: 6686: 6676: 6675: 6669: 6668: 6666: 6665: 6660: 6655: 6649: 6647: 6643: 6642: 6640: 6639: 6634: 6633: 6632: 6622: 6621: 6620: 6609: 6607: 6601: 6600: 6597: 6596: 6594: 6593: 6584: 6579: 6574: 6569: 6568: 6567: 6562: 6551: 6549: 6547:Immunogenetics 6543: 6542: 6540: 6539: 6534: 6529: 6528: 6527: 6522: 6517: 6512: 6507: 6495: 6494: 6492:Co-stimulation 6489: 6484: 6479: 6474: 6469: 6464: 6459: 6452: 6450: 6444: 6443: 6441: 6440: 6435: 6433:Immune complex 6429: 6428: 6423: 6418: 6413: 6408: 6407: 6406: 6401: 6396: 6391: 6380: 6378: 6374: 6373: 6371: 6370: 6365: 6360: 6355: 6353:Dendritic cell 6341: 6340: 6335: 6334: 6333: 6331:Conformational 6328: 6317: 6316: 6311: 6310: 6309: 6304: 6299: 6288: 6286: 6279: 6275: 6274: 6262: 6260: 6259: 6252: 6245: 6237: 6228: 6227: 6225: 6224: 6219: 6214: 6208: 6206: 6200: 6199: 6196: 6195: 6193: 6192: 6187: 6182: 6181: 6180: 6170: 6164: 6161: 6160: 6158: 6157: 6152: 6147: 6142: 6137: 6131: 6129: 6120: 6114: 6113: 6110: 6109: 6107: 6106: 6101: 6096: 6090: 6088: 6082: 6081: 6079: 6078: 6077: 6076: 6072: 6068: 6064: 6060: 6056: 6052: 6048: 6039: 6034: 6024: 6016: 6009: 6001: 5995: 5989: 5983: 5977: 5976: 5974: 5973: 5968: 5963: 5962: 5961: 5951: 5947: 5942: 5937: 5932: 5927: 5922: 5917: 5912: 5906: 5904: 5898: 5897: 5892: 5890: 5889: 5882: 5875: 5867: 5860: 5859: 5837: 5831: 5815: 5813: 5810: 5807: 5806: 5747: 5722: 5673: 5637: 5618:(2): 105–106. 5602: 5545: 5494: 5444: 5415:(3): 618–622. 5395: 5366:(9): 2431–42. 5345: 5324:(3): 1171–81. 5304: 5283:(4): 1838–48. 5263: 5236:(9): 1339–47. 5213: 5184:(7): 1711–20. 5164: 5115: 5072: 5023: 4974: 4922: 4871: 4842:(9): 1905–18. 4822: 4773: 4724: 4701:10.1038/nm1492 4695:(11): 1301–9. 4675: 4624: 4581: 4532: 4483: 4432: 4383: 4334: 4297:PLOS Pathogens 4278: 4254: 4247: 4224: 4204: 4169:Trends Immunol 4155: 4103: 4052: 4027: 3998:(3): 1042–52. 3978: 3935: 3928: 3907: 3858: 3849: 3826:10.1038/ni1105 3800: 3749: 3698: 3663: 3646: 3587: 3538: 3499:(20): 8290–5. 3479: 3430: 3395: 3346: 3290: 3239: 3188: 3159:(8–9): 742–8. 3139: 3081: 3052:(5): 2171–80. 3032: 2981: 2938: 2897: 2848: 2798: 2749: 2700: 2649: 2597: 2548: 2497: 2482: 2456: 2427:(7): 634–643. 2404: 2353: 2324:(5): 1119–27. 2304: 2269: 2262: 2244: 2194: 2167:(6): 512–519. 2144: 2115:(5): 627–636. 2095: 2076:(1): 139–176. 2060: 2001: 1994: 1976: 1947:(3): 619–631. 1927: 1886: 1835: 1813: 1791: 1760: 1759: 1757: 1754: 1753: 1752: 1746: 1741: 1736: 1731: 1724: 1721: 1709: 1706: 1695: 1692: 1661: 1658: 1623: 1622: 1600: 1598: 1591: 1585: 1582: 1581: 1580: 1575: 1570: 1557: 1530: 1527: 1470:Omenn syndrome 1435:Main article: 1432: 1429: 1427: 1424: 1414: 1411: 1195:co-stimulation 1156: 1153: 1102:Main article: 1099: 1096: 1044:Main article: 1041: 1038: 1007:Main article: 1004: 1001: 988: 985: 939: 935: 931: 910:Main article: 907: 904: 903: 902: 898: 892: 888: 884: 878: 874: 862: 858: 855: 835: 807:Main article: 804: 803:Memory T cells 801: 779: 761:Main article: 758: 755: 752: 751: 748: 745: 742: 739: 735: 734: 731: 728: 725: 722: 716: 715: 712: 709: 706: 703: 697: 696: 693: 690: 687: 684: 678: 677: 674: 671: 668: 665: 659: 658: 655: 652: 647: 641: 635: 634: 631: 628: 625: 622: 575:memory B cells 562: 559:T helper cells 544:Main article: 541: 538: 536: 533: 527: 524: 518: 515: 510: 507: 456: 453: 412: 409: 391: 388: 363:Main article: 360: 357: 295:lymphoid cells 274: 271: 269: 266: 243: 240:memory B cells 235: 153: 152: 143: 137: 136: 131: 125: 124: 119: 113: 112: 107: 101: 100: 95: 89: 88: 84: 83: 78: 72: 71: 67: 66: 58:red blood cell 55: 47: 46: 43: 35: 34: 26: 24: 14: 13: 10: 9: 6: 4: 3: 2: 6711: 6700: 6697: 6695: 6694:Immune system 6692: 6690: 6687: 6685: 6682: 6681: 6679: 6664: 6661: 6659: 6656: 6654: 6651: 6650: 6648: 6644: 6638: 6635: 6631: 6628: 6627: 6626: 6623: 6619: 6616: 6615: 6614: 6611: 6610: 6608: 6606: 6602: 6592: 6588: 6585: 6583: 6580: 6578: 6575: 6573: 6570: 6566: 6563: 6561: 6558: 6557: 6556: 6553: 6552: 6550: 6548: 6544: 6538: 6535: 6533: 6530: 6526: 6523: 6521: 6518: 6516: 6515:Clonal anergy 6513: 6511: 6508: 6506: 6503: 6502: 6501: 6497: 6496: 6493: 6490: 6488: 6485: 6483: 6480: 6478: 6475: 6473: 6470: 6468: 6465: 6463: 6460: 6458: 6454: 6453: 6451: 6445: 6439: 6436: 6434: 6431: 6430: 6427: 6424: 6422: 6419: 6417: 6414: 6412: 6409: 6405: 6404:Microantibody 6402: 6400: 6397: 6395: 6392: 6390: 6387: 6386: 6385: 6382: 6381: 6379: 6375: 6369: 6366: 6364: 6361: 6359: 6356: 6354: 6350: 6346: 6343: 6342: 6339: 6336: 6332: 6329: 6327: 6324: 6323: 6322: 6319: 6318: 6315: 6312: 6308: 6305: 6303: 6300: 6298: 6295: 6294: 6293: 6290: 6289: 6287: 6283: 6280: 6276: 6272: 6268: 6265: 6258: 6253: 6251: 6246: 6244: 6239: 6238: 6235: 6223: 6222:Prolymphocyte 6220: 6218: 6215: 6213: 6210: 6209: 6207: 6205: 6204:Lymphopoiesis 6201: 6191: 6188: 6186: 6183: 6179: 6176: 6175: 6174: 6171: 6169: 6166: 6165: 6162: 6156: 6153: 6151: 6148: 6146: 6143: 6141: 6138: 6136: 6133: 6132: 6130: 6128: 6124: 6121: 6119: 6115: 6105: 6102: 6100: 6097: 6095: 6092: 6091: 6089: 6087: 6083: 6075: 6069: 6067: 6061: 6059: 6053: 6051: 6045: 6044: 6043: 6042:Memory T cell 6040: 6038: 6035: 6032: 6028: 6020: 6012: 6005: 6002: 6000: 5999:Cytotoxic CD8 5996: 5994: 5991: 5990: 5987: 5984: 5982: 5978: 5972: 5969: 5967: 5964: 5960: 5957: 5956: 5955: 5948: 5946: 5943: 5941: 5938: 5936: 5935:Marginal zone 5933: 5931: 5928: 5926: 5923: 5921: 5918: 5916: 5913: 5911: 5908: 5907: 5905: 5903: 5899: 5895: 5888: 5883: 5881: 5876: 5874: 5869: 5868: 5865: 5853: 5849: 5842: 5838: 5834: 5828: 5824: 5823: 5817: 5816: 5811: 5802: 5798: 5793: 5788: 5783: 5778: 5774: 5770: 5766: 5762: 5758: 5751: 5748: 5736: 5732: 5726: 5723: 5718: 5714: 5709: 5704: 5700: 5696: 5692: 5688: 5684: 5677: 5674: 5669: 5665: 5661: 5657: 5653: 5649: 5641: 5638: 5633: 5629: 5625: 5621: 5617: 5613: 5606: 5603: 5598: 5594: 5589: 5584: 5580: 5576: 5572: 5568: 5564: 5560: 5556: 5549: 5546: 5541: 5537: 5532: 5527: 5522: 5517: 5513: 5509: 5505: 5498: 5495: 5490: 5486: 5481: 5476: 5472: 5468: 5465:(4): 917–27. 5464: 5460: 5456: 5448: 5445: 5440: 5436: 5431: 5426: 5422: 5418: 5414: 5410: 5406: 5399: 5396: 5391: 5387: 5383: 5379: 5374: 5369: 5365: 5361: 5357: 5349: 5346: 5341: 5337: 5332: 5327: 5323: 5319: 5315: 5308: 5305: 5300: 5296: 5291: 5286: 5282: 5278: 5274: 5267: 5264: 5259: 5255: 5251: 5247: 5243: 5239: 5235: 5231: 5224: 5217: 5214: 5209: 5205: 5200: 5195: 5191: 5187: 5183: 5179: 5175: 5168: 5165: 5160: 5156: 5151: 5146: 5142: 5138: 5134: 5130: 5126: 5119: 5116: 5111: 5107: 5103: 5099: 5095: 5091: 5087: 5083: 5076: 5073: 5068: 5064: 5059: 5054: 5050: 5046: 5042: 5038: 5034: 5027: 5024: 5019: 5015: 5010: 5005: 5001: 4997: 4993: 4989: 4985: 4978: 4975: 4970: 4966: 4961: 4956: 4952: 4948: 4944: 4940: 4936: 4929: 4927: 4923: 4918: 4914: 4909: 4904: 4899: 4894: 4890: 4886: 4885:Critical Care 4882: 4875: 4872: 4867: 4863: 4858: 4853: 4849: 4845: 4841: 4837: 4833: 4826: 4823: 4818: 4814: 4809: 4804: 4800: 4796: 4793:(1): 182–96. 4792: 4788: 4784: 4777: 4774: 4769: 4765: 4760: 4755: 4751: 4747: 4744:(1): 145–57. 4743: 4739: 4735: 4728: 4725: 4720: 4716: 4711: 4706: 4702: 4698: 4694: 4690: 4686: 4679: 4676: 4671: 4667: 4662: 4657: 4652: 4647: 4643: 4639: 4635: 4628: 4625: 4620: 4616: 4612: 4608: 4604: 4600: 4596: 4592: 4585: 4582: 4577: 4573: 4568: 4563: 4559: 4555: 4551: 4547: 4543: 4536: 4533: 4528: 4524: 4519: 4514: 4510: 4506: 4502: 4498: 4494: 4487: 4484: 4479: 4475: 4470: 4465: 4460: 4455: 4451: 4447: 4446:Front Immunol 4443: 4436: 4433: 4428: 4424: 4419: 4414: 4410: 4406: 4403:(4): 474–81. 4402: 4398: 4394: 4387: 4384: 4379: 4375: 4370: 4365: 4361: 4357: 4353: 4349: 4345: 4338: 4335: 4330: 4326: 4321: 4316: 4311: 4306: 4302: 4298: 4294: 4287: 4285: 4283: 4279: 4264: 4258: 4255: 4250: 4244: 4240: 4239: 4231: 4229: 4225: 4222: 4218: 4217: 4211: 4209: 4205: 4200: 4196: 4191: 4186: 4182: 4178: 4174: 4170: 4166: 4159: 4156: 4151: 4147: 4142: 4137: 4133: 4129: 4126:(3): 619–31. 4125: 4121: 4117: 4110: 4108: 4104: 4099: 4095: 4090: 4085: 4080: 4075: 4071: 4067: 4063: 4056: 4053: 4042: 4038: 4031: 4028: 4023: 4019: 4014: 4009: 4005: 4001: 3997: 3993: 3989: 3982: 3979: 3974: 3970: 3966: 3962: 3958: 3954: 3950: 3946: 3939: 3936: 3931: 3925: 3921: 3914: 3912: 3908: 3903: 3899: 3894: 3889: 3885: 3881: 3877: 3873: 3869: 3862: 3859: 3853: 3850: 3845: 3841: 3836: 3831: 3827: 3823: 3820:(9): 927–33. 3819: 3815: 3811: 3804: 3801: 3796: 3792: 3788: 3784: 3780: 3776: 3772: 3768: 3764: 3760: 3753: 3750: 3745: 3741: 3737: 3733: 3729: 3725: 3721: 3717: 3713: 3709: 3702: 3699: 3694: 3690: 3686: 3682: 3679:(1): 171–92. 3678: 3674: 3667: 3664: 3660: 3656: 3650: 3647: 3642: 3638: 3634: 3630: 3626: 3622: 3618: 3614: 3610: 3606: 3599: 3591: 3588: 3583: 3579: 3575: 3571: 3566: 3561: 3557: 3553: 3549: 3542: 3539: 3534: 3530: 3525: 3520: 3515: 3510: 3506: 3502: 3498: 3494: 3490: 3483: 3480: 3475: 3471: 3466: 3461: 3457: 3453: 3450:(2): 266–74. 3449: 3445: 3441: 3434: 3431: 3426: 3422: 3418: 3414: 3410: 3406: 3399: 3396: 3391: 3387: 3382: 3377: 3373: 3369: 3365: 3361: 3357: 3350: 3347: 3342: 3338: 3333: 3328: 3323: 3318: 3314: 3310: 3306: 3299: 3297: 3295: 3291: 3286: 3282: 3277: 3272: 3267: 3262: 3258: 3254: 3250: 3243: 3240: 3235: 3231: 3226: 3221: 3216: 3211: 3207: 3203: 3199: 3192: 3189: 3184: 3180: 3175: 3170: 3166: 3162: 3158: 3154: 3150: 3143: 3140: 3135: 3131: 3126: 3121: 3116: 3111: 3107: 3103: 3099: 3092: 3090: 3088: 3086: 3082: 3077: 3073: 3068: 3063: 3059: 3055: 3051: 3047: 3043: 3036: 3033: 3028: 3024: 3019: 3014: 3009: 3004: 3000: 2996: 2992: 2985: 2982: 2977: 2973: 2969: 2965: 2961: 2957: 2953: 2949: 2942: 2939: 2934: 2930: 2925: 2920: 2916: 2912: 2908: 2901: 2898: 2893: 2889: 2885: 2881: 2876: 2871: 2867: 2863: 2859: 2852: 2849: 2844: 2840: 2835: 2830: 2826: 2822: 2818: 2814: 2810: 2802: 2799: 2794: 2790: 2785: 2780: 2776: 2772: 2768: 2764: 2760: 2753: 2750: 2745: 2741: 2736: 2731: 2727: 2723: 2720:(1): 165–81. 2719: 2715: 2711: 2704: 2701: 2696: 2692: 2687: 2682: 2677: 2672: 2668: 2664: 2660: 2653: 2650: 2645: 2641: 2637: 2633: 2628: 2623: 2619: 2615: 2608: 2601: 2598: 2593: 2589: 2585: 2581: 2576: 2571: 2568:(7): 2171–8. 2567: 2563: 2559: 2552: 2549: 2544: 2540: 2536: 2532: 2528: 2527:10.1038/44385 2524: 2520: 2516: 2512: 2508: 2501: 2498: 2493: 2489: 2485: 2479: 2475: 2471: 2467: 2460: 2457: 2452: 2448: 2443: 2438: 2434: 2430: 2426: 2422: 2418: 2411: 2409: 2405: 2400: 2396: 2391: 2386: 2381: 2376: 2372: 2368: 2364: 2357: 2354: 2349: 2345: 2340: 2335: 2331: 2327: 2323: 2319: 2315: 2308: 2305: 2300: 2296: 2292: 2288: 2284: 2280: 2273: 2270: 2265: 2263:9780815342434 2259: 2255: 2248: 2245: 2240: 2236: 2231: 2226: 2222: 2218: 2214: 2210: 2206: 2198: 2195: 2190: 2186: 2182: 2178: 2174: 2170: 2166: 2162: 2155: 2148: 2145: 2140: 2136: 2132: 2128: 2123: 2118: 2114: 2110: 2106: 2099: 2096: 2091: 2087: 2083: 2079: 2075: 2071: 2064: 2061: 2056: 2052: 2047: 2042: 2037: 2032: 2028: 2024: 2020: 2016: 2012: 2005: 2002: 1997: 1995:9780815342434 1991: 1987: 1980: 1977: 1972: 1968: 1963: 1958: 1954: 1950: 1946: 1942: 1938: 1931: 1928: 1923: 1919: 1914: 1909: 1905: 1901: 1897: 1890: 1887: 1882: 1878: 1873: 1868: 1863: 1858: 1854: 1850: 1846: 1839: 1836: 1832: 1828: 1824: 1817: 1814: 1809: 1805: 1798: 1796: 1792: 1779: 1775: 1771: 1765: 1762: 1755: 1750: 1747: 1745: 1742: 1740: 1737: 1735: 1732: 1730: 1727: 1726: 1722: 1720: 1715: 1708:During cancer 1707: 1705: 1702: 1693: 1691: 1688: 1684: 1680: 1676: 1672: 1668: 1659: 1657: 1655: 1651: 1647: 1643: 1639: 1635: 1629: 1619: 1614: 1610: 1609: 1604: 1599: 1590: 1589: 1583: 1579: 1576: 1574: 1571: 1569: 1565: 1561: 1558: 1556: 1553: 1552: 1551: 1549: 1545: 1541: 1536: 1528: 1526: 1524: 1520: 1519: 1514: 1513: 1512:Mycobacterium 1508: 1507: 1502: 1497: 1495: 1491: 1487: 1483: 1479: 1475: 1471: 1467: 1463: 1459: 1455: 1447: 1443: 1438: 1430: 1425: 1423: 1420: 1412: 1410: 1408: 1403: 1401: 1397: 1393: 1388: 1384: 1382: 1378: 1374: 1373:NF-κB pathway 1369: 1367: 1363: 1359: 1354: 1350: 1346: 1342: 1338: 1334: 1330: 1326: 1322: 1318: 1314: 1309: 1307: 1303: 1299: 1295: 1291: 1287: 1283: 1279: 1275: 1271: 1266: 1264: 1260: 1256: 1252: 1248: 1244: 1240: 1234: 1232: 1227: 1224: 1220: 1216: 1212: 1208: 1204: 1200: 1196: 1192: 1188: 1184: 1180: 1176: 1167: 1162: 1154: 1152: 1150: 1146: 1142: 1138: 1134: 1130: 1126: 1122: 1118: 1114: 1110: 1105: 1097: 1095: 1093: 1089: 1085: 1081: 1077: 1073: 1069: 1065: 1061: 1057: 1053: 1047: 1039: 1037: 1035: 1031: 1027: 1023: 1019: 1015: 1010: 1002: 1000: 997: 993: 986: 984: 982: 978: 974: 970: 965: 963: 960: 956: 952: 949: 943: 928: 926: 922: 918: 913: 905: 896: 893: 882: 879: 872: 868: 856: 853: 849: 845: 841: 833: 832: 831: 828: 826: 821: 820:memory T cell 816: 810: 809:Memory T cell 802: 800: 797: 793: 789: 785: 777: 769: 764: 756: 749: 746: 743: 740: 737: 736: 732: 729: 726: 723: 721: 718: 717: 713: 710: 707: 704: 702: 699: 698: 694: 691: 688: 685: 683: 680: 679: 675: 672: 669: 666: 664: 661: 660: 656: 653: 651: 648: 645: 642: 640: 637: 636: 632: 629: 626: 623: 620: 619: 613: 611: 607: 603: 599: 596: 592: 588: 584: 580: 576: 572: 568: 560: 552: 547: 546:T helper cell 539: 534: 532: 525: 523: 517:Thymic output 516: 514: 508: 506: 504: 500: 499:naive T cells 496: 492: 487: 483: 479: 475: 471: 467: 463: 454: 452: 450: 445: 443: 438: 434: 429: 426: 422: 418: 417:thymic cortex 410: 408: 406: 401: 397: 389: 387: 385: 381: 375: 373: 366: 358: 356: 354: 350: 346: 342: 338: 334: 329: 327: 323: 319: 315: 311: 306: 304: 300: 296: 292: 288: 284: 280: 272: 267: 265: 263: 259: 255: 251: 247: 241: 233: 229: 225: 221: 217: 216:CD4+ "helper" 213: 212:CD8+ "killer" 208: 206: 202: 198: 194: 190: 185: 183: 179: 175: 171: 167: 166:immune system 163: 159: 148: 142: 138: 135: 132: 130: 126: 123: 120: 118: 114: 111: 108: 106: 102: 99: 98:lymphocytus T 96: 94: 90: 85: 82: 81:Immune system 79: 77: 73: 68: 63: 59: 53: 48: 41: 36: 31: 19: 6617: 6482:Inflammation 6467:Alloimmunity 6462:Autoimmunity 6447:Immunity vs. 6399:Autoantibody 6297:Superantigen 5980: 5852:the original 5847: 5821: 5764: 5760: 5750: 5739:. Retrieved 5737:. 2018-08-21 5734: 5725: 5690: 5686: 5676: 5651: 5647: 5640: 5615: 5611: 5605: 5562: 5558: 5548: 5511: 5507: 5497: 5462: 5458: 5447: 5412: 5408: 5398: 5363: 5359: 5348: 5321: 5317: 5307: 5280: 5276: 5266: 5233: 5229: 5216: 5181: 5177: 5167: 5132: 5128: 5118: 5085: 5081: 5075: 5040: 5036: 5026: 4991: 4987: 4977: 4942: 4938: 4888: 4884: 4874: 4839: 4835: 4825: 4790: 4786: 4776: 4741: 4737: 4727: 4692: 4688: 4678: 4641: 4637: 4627: 4597:(6): 492–9. 4594: 4590: 4584: 4549: 4545: 4535: 4500: 4496: 4486: 4449: 4445: 4435: 4400: 4396: 4386: 4351: 4347: 4337: 4300: 4296: 4270:. Retrieved 4257: 4237: 4214: 4175:(4): 153–8. 4172: 4168: 4158: 4123: 4120:Mol. Immunol 4119: 4069: 4065: 4055: 4044:. Retrieved 4040: 4030: 3995: 3991: 3981: 3948: 3944: 3938: 3919: 3875: 3871: 3861: 3852: 3817: 3813: 3803: 3762: 3758: 3752: 3711: 3707: 3701: 3676: 3672: 3666: 3649: 3608: 3604: 3590: 3558:(8): 767–9. 3555: 3551: 3541: 3496: 3492: 3482: 3447: 3443: 3433: 3408: 3404: 3398: 3363: 3359: 3349: 3312: 3308: 3256: 3252: 3242: 3205: 3201: 3191: 3156: 3152: 3142: 3105: 3101: 3049: 3045: 3035: 2998: 2994: 2984: 2951: 2947: 2941: 2917:(5): 591–4. 2914: 2910: 2900: 2868:(4): 307–8. 2865: 2862:Nat. Immunol 2861: 2851: 2816: 2812: 2801: 2769:(2): 50–56. 2766: 2762: 2752: 2717: 2713: 2703: 2666: 2662: 2652: 2617: 2613: 2600: 2565: 2561: 2551: 2510: 2506: 2500: 2465: 2459: 2424: 2420: 2370: 2366: 2356: 2321: 2317: 2307: 2282: 2278: 2272: 2253: 2247: 2212: 2208: 2197: 2164: 2160: 2147: 2112: 2108: 2098: 2073: 2069: 2063: 2018: 2014: 2004: 1985: 1979: 1944: 1940: 1930: 1903: 1899: 1889: 1852: 1848: 1838: 1830: 1826: 1816: 1807: 1782:. Retrieved 1778:the original 1773: 1764: 1717: 1697: 1663: 1630: 1626: 1617: 1606: 1538: 1516: 1510: 1504: 1503:, including 1498: 1451: 1416: 1404: 1400:SpaceX CRS-3 1389: 1385: 1370: 1310: 1277: 1273: 1267: 1235: 1228: 1172: 1107: 1049: 1012: 995: 991: 990: 979:. Recently, 966: 954: 944: 929: 915: 842:(CCR7), and 829: 812: 774: 602:MHC class II 586: 571:plasma cells 557: 529: 520: 512: 485: 474:phagocytosed 469: 458: 449:autoimmunity 446: 441: 436: 432: 430: 414: 404: 393: 376: 368: 352: 330: 325: 322:downregulate 309: 307: 276: 258:immune cells 248: 209: 186: 182:cell surface 157: 156: 97: 6689:Human cells 6605:Lymphocytes 6264:Lymphocytic 6217:Lymphoblast 5915:Plasmablast 5894:Lymphocytes 5693:(7): e330. 4891:(4): R183. 3878:(6): 1–13. 3872:J Autoimmun 3366:(1): 1–12. 3001:: 6633824. 2285:: 529–560. 2209:JCI Insight 1784:21 December 1739:Immunoblast 1358:calcineurin 1241:-bodies or 1060:MHC class I 861:cells and T 852:lymph nodes 796:MHC class I 792:amino acids 724:IL-21, IL-4 587:CD4 T cells 583:macrophages 268:Development 193:bone marrow 174:lymphocytes 87:Identifiers 6699:Immunology 6678:Categories 6646:Substances 6510:Peripheral 6498:Inaction: 6377:Antibodies 6358:Macrophage 6271:complement 6031:Regulatory 6004:Helper CD4 5930:Follicular 5741:2018-09-22 5565:(1): 948. 5514:(1): 116. 4397:Immunology 4272:2008-04-07 4046:2014-04-14 3360:Immunology 2562:J. Immunol 1855:: 925135. 1756:References 1712:See also: 1618:(May 2023) 1584:Exhaustion 1452:Causes of 1431:Deficiency 1343:and AP-1. 1159:See also: 1155:Activation 1129:isoprenoid 1086:, such as 981:Th17 cells 867:L-selectin 844:L-selectin 784:transplant 708:IRF4, PU.1 303:thymocytes 262:autoimmune 256:, whereby 60:(left), a 6663:Cytolysin 6653:Cytokines 6500:Tolerance 6449:tolerance 6368:Immunogen 6190:LTi cells 6145:Null cell 5993:Thymocyte 5654:: 32–40. 5088:: 78–84. 4994:: 33–39. 4644:(1): 50. 4221:eMedicine 3945:BioEssays 2819:: 76–88. 1492:(AT) and 1298:tyrosines 1211:PH domain 1072:cytokines 1068:vitamin B 1024:with the 621:Cell type 610:cytokines 491:apoptotic 372:pathogens 254:tolerance 232:cytokines 228:cytotoxic 6613:Cellular 6457:Immunity 6455:Action: 6438:Paratope 6426:Idiotype 6416:Allotype 6384:Antibody 6338:Mimotope 6302:Allergen 6285:Antigens 6278:Lymphoid 6178:Nuocytes 6127:NK cells 5959:B10 cell 5801:21576466 5717:26230954 5668:29477343 5632:22189042 5597:29507342 5540:27809856 5489:22186141 5439:29197679 5382:25943855 5340:26963287 5299:26170387 5258:33409478 5250:18475193 5208:25377077 5159:11375065 5110:21657071 5102:29689313 5067:27671246 5018:27993215 4969:22187279 4917:21798063 4866:25113973 4817:23947355 4768:19604493 4738:Immunity 4719:17041596 4670:29914540 4619:11052693 4611:21739672 4576:22623779 4478:29483916 4427:20201977 4378:31570879 4329:34555119 4199:24636916 4150:17825415 4098:26471060 4022:21045195 3973:28521713 3965:14579250 3902:25578468 3844:15300249 3795:38040377 3787:12690201 3736:12594515 3693:17129182 3633:23051753 3582:27717815 3574:20733595 3533:19416870 3474:24450998 3425:28119072 3390:26778581 3341:26136743 3285:25339949 3234:26468291 3183:21458588 3134:26217338 3076:17353286 3027:33506055 2976:30992456 2968:26482978 2933:24434314 2892:11294516 2884:23507634 2843:27894837 2793:21288770 2744:23947354 2695:18657274 2669:(6): 6. 2644:16412760 2636:16237082 2592:22340282 2535:10537110 2492:25261209 2451:30867582 2399:32973809 2373:: 2025. 2348:17476341 2299:10837068 2239:28814669 2189:33154019 2181:20431619 2139:15983629 2090:12414722 2055:24927565 1971:17325202 1922:28002722 1900:Immunity 1881:22474485 1723:See also 1521:. 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