142:
as well as CD8 cells. As a result, there are reduced levels of CD8 cells, which express CD28, in individuals with HIV. With regards to subjects with both
Hepatitis C Virus (HCV) and HIV, levels of CD8 cells are also reduced. CD28 signaling has a large role in the adaptive response to HCV and can increase morbidity for HCV/HIV coinfection within a subject. CD28 induces IL-2 secretion that increases IL-2 mRNA stability. CD28 costimulation influences the expression of key genes expressed in T cell differentiation. Tat, a regulatory protein that regulates viral transcription, increases the transcription of the HIV dsDNA. CD28 costimulation with the Tat protein can contribute to chronic immune hyperactivation seen among HIV-infected individuals. Thus, CD28 is an essential part of therapeutics for the infection and pathogenesis of HIV.
86:
receptors causes epigenetic, transcriptional and post-translational alterations in T cells. Specifically, CD28 costimulation controls many aspects within T cells, one being the expression of proinflammatory cytokine genes. A particular cytokine gene encodes for IL-2, which influences T cell proliferation, survival, and differentiation. The absence of CD28 costimulation results in the loss of IL-2 production causing the T cells to be anergic. Additionally, CD28 ligation causes arginine-methylation for many proteins. CD28 also drives transcription within T cells and produce signals that lead to IL-2 production and Bcl-xL regulation, an antiapoptotic protein, which are essential for T cell survival. CD28 receptors can be seen on 80% of human CD4+ and 50% of CD8+ T cells, in which this percentage decreases with age.
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antiapoptotic gene, and secrete cytokines with the help of CD28 expression. When introduced to mice with pre-existing tumors, these T cells remove the tumors completely. The CD137 presence within the cells maintains the persistence of the engineered T cells. This interaction between engineered T cells with CD28 and CD137 are essential for immunotherapy, and show promise for directing T lymphocytes to tumor antigens and altering the tumor microenvironment for mesothelin.
20:
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Binding CD28 to superantigens can induce an overexpression of inflammatory cytokines which may be harmful. When CD28 interacts with coligand B7-2, these superantigens elicit T-cell hyperactivation. Superantigens can form this overexpression by controlling interactions between MHC-II and TCRs as well
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The CD28 pathway is targeted by the human immunodeficiency virus (HIV) as the virus infects large numbers of normal cells. CD28 has effects on the transcription and stability of interleukin-2 and IFN-γ, cytokines that are important for immunity and stimulating NK cells. HIV alters the CD28 signaling
85:
CD28 receptors aid in other T cell processes such as cytoskeletal remodeling, production of cytokines and chemokines and intracellular biochemical reactions (i.e. phosphorylation, transcriptional signaling, and metabolism) that are key for T cell proliferation and differentiation. Ligation of CD28
76:
CD28 receptors play a role in the development and proliferation of T cells. The CD28 receptors enhance signals from the T cell receptors (TCR) in order to stimulate an immune response and an anti-inflammatory response on regulatory T cells. Through the promotion of T cell function, CD28 receptors
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Additionally, genetically engineered T cells containing CD28 and CD137 can be used in a molecularly targeted therapy response to a type of carcinomas called mesothelin. These T cells have a high affinity for human mesothelin. Upon mesothelin stimulation, the T cells proliferate, express an
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Ott M, Emiliani S, Van Lint C, Herbein G, Lovett J, Chirmule N, et al. (March 1997). "Immune hyperactivation of HIV-1-infected T cells mediated by Tat and the CD28 pathway".
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as increasing the B7-2 and CD28 costimulatory interactions. This is dangerous because the overexpression of inflammatory cytokines can cause toxic shock in an individual.
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allow effector T cells to combat regulatory T cell-mediated suppression from adaptive immunity. CD28 receptors also elicit the prevention of spontaneous autoimmunity.
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Wakamatsu E, Omori H, Ohtsuka S, Ogawa S, Green JM, Abe R (September 2018). "Regulatory T cell subsets are differentially dependent on CD28 for their proliferation".
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The left image is a visual of CD28 attached to a T cell interacting in costimulation with B7 to activate the T cell and promote an immune response.
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Carreno BM, Collins M (2002). "The B7 family of ligands and its receptors: new pathways for costimulation and inhibition of immune responses".
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555:"Control of large, established tumor xenografts with genetically retargeted human T cells containing CD28 and CD137 domains"
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173:"Chapter 16: Costimulatory molecules in T-cell activation and transplantation: Section 2: The CD28 receptor family"
39:
698:"Superantigens hyperinduce inflammatory cytokines by enhancing the B7-2/CD28 costimulatory receptor interaction"
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315:"In the absence of its cytosolic domain, the CD28 molecule still contributes to T cell activation"
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Morin SO, Giroux V, Favre C, Bechah Y, Auphan-Anezin N, Roncagalli R, et al. (July 2015).
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Carreno BM, Collins M (October 2003). "BTLA: a new inhibitory receptor with a B7-like ligand".
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Carpenito C, Milone MC, Hassan R, Simonet JC, Lakhal M, Suhoski MM, et al. (March 2009).
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614:"HIV coinfection impairs CD28-mediated costimulation of hepatitis C virus-specific CD8 cells"
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Yonkers NL, Rodriguez B, Post AB, Asaad R, Jones L, Lederman MM, et al. (August 2006).
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Levy R, Rotfogel Z, Hillman D, Popugailo A, Arad G, Supper E, et al. (October 2016).
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506:"The CD28-B7 Family in Anti-Tumor Immunity: Emerging Concepts in Cancer Immunotherapy"
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of B7 ligands that bind to inhibitory CD28 family member receptors on immune cells.
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Proceedings of the
National Academy of Sciences of the United States of America
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364:"Signals from CD28 induce stable epigenetic modification of the IL-2 promoter"
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Some cancer cells evade destruction by the immune system through an
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Esensten JH, Helou YA, Chopra G, Weiss A, Bluestone JA (May 2016).
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Esensten JH, Helou YA, Chopra G, Weiss A, Bluestone JA (May 2016).
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act as inhibitors. Ligands for the CD28 receptor family include
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454:"CD28 Costimulation: From Mechanism to Therapy"
405:"CD28 Costimulation: From Mechanism to Therapy"
38:. The CD28 family in turn is a subgroup of the
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179:. Boston, MA: Springer US. pp. 292–8.
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16:Group of regulatory cell surface receptors
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362:Thomas RM, Gao L, Wells AD (April 2005).
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249:10.1146/annurev.immunol.20.091101.091806
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177:Immunobiology of Organ Transplantation
175:. In Burlingham WJ, Wilkes DS (eds.).
109:directed against CD28 family members
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319:Cellular and Molecular Life Sciences
146:Hyper-induced inflammatory cytokines
618:The Journal of Infectious Diseases
117:, or their B7 ligands function as
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504:Leung J, Suh WK (December 2014).
53:, act as positive regulators of
57:function while another three,
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667:10.1126/science.275.5305.1481
470:10.1016/j.immuni.2016.04.020
421:10.1016/j.immuni.2016.04.020
284:10.1016/j.molimm.2018.05.021
381:10.4049/jimmunol.174.8.4639
237:Annual Review of Immunology
125:and are clinically used in
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847:Immunoglobulin superfamily
783:Immunoglobulin superfamily
171:Arch RH, Green JM (2012).
40:immunoglobulin superfamily
30:are a group of regulatory
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522:10.4110/in.2014.14.6.265
214:10.1016/j.it.2003.08.005
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580:10.1073/pnas.0813101106
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32:cell surface receptors
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787:CD28 family receptors
368:Journal of Immunology
119:checkpoint inhibitors
90:Clinical significance
28:CD28 family receptors
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272:Molecular Immunology
202:Trends in Immunology
127:cancer immunotherapy
45:Two family members,
714:2016PNAS..113E6437L
708:(42): E6437–E6446.
571:2009PNAS..106.3360C
121:to overcome tumor
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510:Immune Network
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852:Immunology
836:Categories
278:: 92–101.
155:References
107:Antibodies
842:Receptors
794:receptors
243:: 29–53.
71:B7 family
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801:BTLA
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181:ISBN
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