22:
254:
IL-27, together with TGF-Ξ² induces IL-10βproducing regulatory T cells with Tr1-like properties cells. IL-27 alone can induce IL-10-producing Tr1 cells, but in the absence of TGF-Ξ², the cells produce large quantities of both IFN-Ξ³ and IL-10. IL-6 and IL-21 also plays a role in differentiation as
296:
Transplantation research has shown, that donor Tr1 in response to recipient alloantigens, was found to correlate with the absence of GvHD after bone marrow transplantation, while decreased numbers of Tr1 markedly associated with severe GvHD. Decreased levels of IL-10 CD4+ producing cells were also
184:
The suppressing and tolerance-inducing effect of Tr1 cells is mediated mainly by cytokines. The other mechanism as cell to cell contact, modulation of dendritic cells, metabolic disruption and cytolysis is however also available to them. In vivo Tr1 cells need to be activated, to be able to exert
1086:
Awasthi, Amit; Carrier, Yijun; Peron, Jean P. S.; Bettelli, Estelle; Kamanaka, Masahito; Flavell, Richard A.; Kuchroo, Vijay K.; Oukka, Mohamed; Weiner, Howard L. (December 2007). "A dominant function for interleukin 27 in generating interleukin 10-producing anti-inflammatory T cells".
119:-specific T-cell response which is necessary for Tr1 cells antigen specificity. CD49b belongs to the integrin family and is a receptor for many (extracellular) matrix and non-matrix molecules. CD49b provides only little contribution to the differentiation and function of Tr1 cells.
250:
Tr 1 cells are inducible, arising from precursors naive T cells. They can be differentiated ex vivo and in vivo. The ways of Tr1 cells induction in vivo, ex vivo and in vitro differ and also envelop many different approaches but the molecular mechanism appears to be conserved.
457:
Gagliani, Nicola; Magnani, Chiara F.; Huber, Samuel; Gianolini, Monica E.; Pala, Mauro; Licona-Limon, Paula; Guo, Binggege; Herbert, De'Broski R.; Bulfone, Alessandro (June 2013). "Coexpression of CD49b and LAG-3 identifies human and mouse T regulatory type 1 cells".
98:. Tr1 cells regulate tolerance towards antigens of any origin. Tr1 cells are self or non-self antigen specific and their key role is to induce and maintain peripheral tolerance and suppress tissue inflammation in autoimmunity and graft vs. host disease.
834:
Manavalan, John S.; Rossi, Paola C.; Vlad, George; Piazza, Flavia; Yarilina, Anna; Cortesini, Raffaello; Mancini, Donna; Suciu-Foca, Nicole (July 2003). "High expression of ILT3 and ILT4 is a general feature of tolerogenic dendritic cells".
782:
Scott-Taylor, Tim H.; O'B Hourihane, Jonathan; Strobel, Stephan (September 2010). "Correlation of allergen-specific IgG subclass antibodies and T lymphocyte cytokine responses in children with multiple food allergies".
106:
The specific cell-surface markers for Tr1 cells in humans and mice are CD4 CD49bLAG-3 CD226 from which LAG-3 and CD49b are indispensable. LAG-3 is a membrane protein on Tr1 cells that negatively regulates
208:. IL-10 indirectly downregulates MHC II molecules and co-stimulatory molecules on antigen-presenting cells (APC) and force them to upregulate tolerogenic molecules such as ILT-3, ILT-4 and HLA-G.
133:
but only transiently, upon their activation and in smaller amounts than CD25 FOXP3 regulatory cells. FOXP3 is not required for Tr1 induction, nor for its function. They also express repressor of
200:
Tr1 cells secrete large amount of suppressing cytokines IL-10 and TGF-Ξ². IL-10 directly inhibits T cells by blocking its production of IL-2, IFN-Ξ³ and GM-CSF and have tolerogenic effect on
122:
They characteristically produce high levels of IL-10, IFN-Ξ³, IL-5 and also TGF- Ξ² but neither IL-4 nor IL-2. Production of IL-10 is also much more rapid than its production by other
927:
Mandapathil, Magis; Szczepanski, Miroslaw J.; Szajnik, Marta; Ren, Jin; Jackson, Edwin K.; Johnson, Jonas T.; Gorelik, Elieser; Lang, Stephan; Whiteside, Theresa L. (2010-09-03).
228:
Tr1 cells can express ectoenzymes CD39 and CD73 and are suspected of generating adenosine which suppresses effector T cell proliferation and their cytokine production in vitro.
511:"A soluble lymphocyte activation gene-3 molecule used as a vaccine adjuvant elicits greater humoral and cellular immune responses to both particulate and soluble antigens"
300:
Phase I/II of clinical trials of Tr1 cell treatment concerning Crohn's disease have been successful and appear to be safe and do not lead to a general immune suppression.
725:
Cobbold, Stephen P.; Nolan, Kathleen F.; Graca, Luis; Castejon, Raquel; Le Moine, Alain; Frewin, Mark; Humm, Susan; Adams, Elizabeth; Thompson, Sara (December 2003).
1334:
Weston, L. E.; Geczy, A. F.; Briscoe, H. (2005-11-07). "Production of IL-10 by alloreactive sibling donor cells and its influence on the development of acute GVHD".
242:
origin, but not other APC or T or B lymphocytes. Cytolysis indirectly suppresses immune response by reducing numbers of myeloid-origin antigen presenting cells.
1222:
Bluestone, Jeffrey A.; Thomson, Angus W.; Shevach, Ethan M.; Weiner, Howard L. (August 2007). "What does the future hold for cell-based tolerogenic therapy?".
1139:"Suppression of autoimmune inflammation of the central nervous system by interleukin 10 secreted by interleukin 27-stimulated T cells (PDF Download Available)"
1278:
Roncarolo, Maria-Grazia; Battaglia, Manuela (August 2007). "Regulatory T-cell immunotherapy for tolerance to self antigens and alloantigens in humans".
293:, allograft rejection, autoimmunity and chronic inflammatory diseases. The first successful tests were performed on mouse models and on humans as well.
238:
Tr1 cells can both express
Granzyme A and granzyme B. It was shown recently, that Tr1 cells, in vitro and also ex vivo, specifically lyse cells of
1043:
Battaglia, Manuela; Gregori, Silvia; Bacchetta, Rosa; Roncarolo, Maria-Grazia (April 2006). "Tr1 cells: from discovery to their clinical application".
255:
they regulate expression of transcription factors necessary for IL-10 production, which is believed to start up the differentiation itself later on.
986:
Magnani, Chiara F.; Alberigo, Giada; Bacchetta, Rosa; Serafini, Giorgia; Andreani, Marco; Roncarolo, Maria Grazia; Gregori, Silvia (June 2011).
40:
715:
Gregori et al.: Type 1 regulatory T (Tr1) cells: from the bench to the bedside. Journal of
Translational Medicine 2012 10(Suppl 3):I7.
878:
Bacchetta, Rosa; Sartirana, Claudia; Levings, Megan K.; Bordignon, Claudio; Narula, Satwant; Roncarolo, Maria-Grazia (August 2002).
662:"Reduced expression of the regulatory CD4+ T cell subset is related to Th1/Th2 balance and disease severity in rheumatoid arthritis"
410:
58:
896:
879:
289:
Tr1 cells possess huge clinical potential in means to prevent, block and even cure several T cells mediated diseases, including
880:"Growth and expansion of human T regulatory type 1 cells are independent from TCR activation but require exogenous cytokines"
678:
661:
558:
Triebel, FrΓ©dΓ©ric (December 2003). "LAG-3: a regulator of T-cell and DC responses and its use in therapeutic vaccination".
137:(ROG), while CD25 FOXP3 regulatory cells do not. ROG then downregulates GATA-3, a characteristic transcription factor for
929:"Adenosine and prostaglandin E2 cooperate in the suppression of immune responses mediated by adaptive regulatory T cells"
988:"Killing of myeloid APCs via HLA class I, CD2 and CD226 defines a novel mechanism of suppression by human Tr1 cells"
144:
Tr1 cells express high levels of regulatory factors, such as glucocorticoid-induced tumor necrosis factor receptor (
290:
239:
1393:
323:
218:
Type 1 regulatory T cells poses inhibitory receptor CTLA-4 through which they exert suppressor function.
1383:
727:"Regulatory T cells and dendritic cells in transplantation tolerance: molecular markers and mechanisms"
1388:
281:
Expression of these transcriptional factors are driven by IL-6 in IL-21 and IL-2 dependant manner.
1311:
1255:
1120:
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491:
161:
91:
328:"The Cellular and Molecular Mechanisms of Immuno-Suppression by Human Type 1 Regulatory T Cells"
385:
Chihara, Norio; Madi, Asaf; Karwacz, Katarzyna; Awasthi, Amit; Kuchroo, Vijay K. (2016-04-01).
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176:. Upon activation, Tr1 cells migrate preferentially in response to I-309, a ligand for CCR8.
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observed in inflamed synovium and peripheral blood of patients with rheumatoid arthritis.
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608:"T-regulatory 1 cells: a novel subset of CD4 T cells with immunoregulatory properties"
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Proposed transcription biomarkers for type 1 regulatory cells differentiation are
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Yudoh, K.; Matsuno, H.; Nakazawa, F.; Yonezawa, T.; Kimura, T. (March 2000).
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1167:"Type 1 regulatory T cells: a new mechanism of peripheral immune tolerance"
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10.1002/1521-4141(200208)32:8<2237::AID-IMMU2237>3.0.CO;2-2
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Zeng, Hanyu; Zhang, Rong; Jin, Boquan; Chen, Lihua (September 2015).
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10.1002/1529-0131(200003)43:3<617::AID-ANR19>3.0.CO;2-B
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provides insufficient context for those unfamiliar with the subject
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15:
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participating in peripheral immunity as a subset of CD4+
111:-mediated signal transduction in cells. LAG-3 activates
36:
387:"Differentiation and Characterization of Tr1 Cells"
160:). Resting human Tr1 cells express Th1 associated
655:
653:
651:
612:The Journal of Allergy and Clinical Immunology
606:Levings, M. K.; Roncarolo, M. G. (July 2000).
8:
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59:Learn how and when to remove this message
129:Tr1 cells do not constitutively express
309:
277:early growth response protein 2 (Egr-2)
156:), and tumor-necrosis factor receptor (
509:El Mir, S.; Triebel, F. (2000-06-01).
285:Clinical manifestation and application
265:musculoaponeurotic fibrosarcoma(c-Maf)
102:Characterization and surface molecules
1329:
1327:
1325:
1273:
1271:
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271:interferon regulatory factor 4 (IRF4)
204:and support differentiation of other
180:Mechanism of Tr1-mediated suppression
41:providing more context for the reader
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1171:Cellular & Molecular Immunology
933:The Journal of Biological Chemistry
268:the aryl hydrocarbon receptor (AhR)
322:Gregori, Silvia; Goudy, Kevin S.;
14:
797:10.1111/j.1399-3038.2010.01025.x
785:Pediatric Allergy and Immunology
744:10.1046/j.1600-065X.2003.00078.x
20:
391:Current Protocols in Immunology
992:European Journal of Immunology
884:European Journal of Immunology
1:
849:10.1016/S0966-3274(03)00058-3
403:10.1002/0471142735.im0327s113
274:the repressor of GATA-3 (ROG)
528:10.4049/jimmunol.164.11.5583
1336:Bone Marrow Transplantation
168:, and Th2-associated CCR3,
1410:
1280:Nature Reviews. Immunology
1224:Nature Reviews. Immunology
1057:10.1016/j.smim.2006.01.007
185:their regulatory effects.
189:Mechanisms of suppression
666:Arthritis and Rheumatism
572:10.1016/j.it.2003.10.001
345:10.3389/fimmu.2012.00030
946:10.1074/jbc.M110.127100
625:10.1067/mai.2000.106635
332:Frontiers in Immunology
324:Roncarolo, Maria Grazia
115:(DCs) and enhances the
72:Type 1 regulatory cells
1348:10.1038/sj.bmt.1705218
1045:Seminars in Immunology
1004:10.1002/eji.201041120
837:Transplant Immunology
731:Immunological Reviews
515:Journal of Immunology
223:Metabolic disruption:
213:Cell to cell contact:
618:(1 Pt 2): S109β112.
560:Trends in Immunology
1183:10.1038/cmi.2015.44
939:(36): 27571β27580.
233:Cytolitic activity:
162:chemokine receptors
37:improve the article
397:: 3.27.1β3.27.10.
206:regulatory T cells
195:Cytokines mediated
92:regulatory T cells
1095:(12): 1380β1389.
1089:Nature Immunology
521:(11): 5583β5589.
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566:(12): 619β622.
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460:Nature Medicine
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113:dendritic cells
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326:(2012-02-29).
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35:Please help
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737:: 109β124.
1389:Immunology
1378:Categories
1148:2017-08-18
304:References
164:CXCR3 and
49:April 2018
1356:0268-3369
1300:1474-1733
1244:1474-1733
1191:2042-0226
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688:0004-3591
634:0091-6749
580:1471-4906
537:0022-1767
480:1546-170X
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354:1664-3224
139:Th2 cells
1364:16284610
1308:17653126
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1125:42502229
1117:17994022
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372:22566914
124:T-helper
1316:7043844
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1021:3116154
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363:3342353
240:myeloid
202:B cells
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96:T cells
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1256:S2CID
1121:S2CID
817:S2CID
765:S2CID
492:S2CID
154:CD134
131:FOXP3
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1352:ISSN
1304:PMID
1296:ISSN
1248:PMID
1240:ISSN
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1187:ISSN
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1105:ISSN
1069:PMID
1061:ISSN
1026:PMID
1008:ISSN
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951:ISSN
910:PMID
902:ISSN
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853:ISSN
809:PMID
801:ISSN
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576:ISSN
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533:ISSN
484:PMID
476:ISSN
435:PMID
417:ISSN
407:ISBN
368:PMID
350:ISSN
291:GvHD
174:CCR8
172:and
170:CCR4
166:CCR5
150:OX40
146:GITR
1344:doi
1288:doi
1232:doi
1195:PMC
1179:doi
1097:doi
1053:doi
1016:PMC
1000:doi
959:PMC
941:doi
937:285
892:doi
845:doi
793:doi
739:doi
735:196
674:doi
620:doi
616:106
568:doi
523:doi
519:164
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