Journal ArticleDOI
Naturally Arising CD4+ Regulatory T Cells for Immunologic Self-Tolerance and Negative Control of Immune Responses
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TLDR
How naturally arising CD25+CD4+ regulatory T cells contribute to the maintenance of immunologic self-tolerance and negative control of various immune responses, and how they can be exploited to prevent and treat autoimmune disease, allergy, cancer, and chronic infection, or establish donor-specific transplantation tolerance are discussed.Abstract:
▪ Abstract Naturally occurring CD4+ regulatory T cells, the majority of which express CD25, are engaged in dominant control of self-reactive T cells, contributing to the maintenance of immunologic self-tolerance. Their depletion or functional alteration leads to the development of autoimmune disease in otherwise normal animals. The majority, if not all, of such CD25+CD4+ regulatory T cells are produced by the normal thymus as a functionally distinct and mature subpopulation of T cells. Their repertoire of antigen specificities is as broad as that of naive T cells, and they are capable of recognizing both self and nonself antigens, thus enabling them to control various immune responses. In addition to antigen recognition, signals through various accessory molecules and via cytokines control their activation, expansion, and survival, and tune their suppressive activity. Furthermore, the generation of CD25+CD4+ regulatory T cells in the immune system is at least in part developmentally and genetically contro...read more
Citations
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Journal ArticleDOI
Reciprocal developmental pathways for the generation of pathogenic effector TH17 and regulatory T cells.
Estelle Bettelli,Yijun Carrier,Wenda Gao,Thomas Korn,Terry B. Strom,Mohamed Oukka,Howard L. Weiner,Vijay K. Kuchroo +7 more
TL;DR: It is shown that IL-6, an acute phase protein induced during inflammation, completely inhibits the generation of Foxp3+ Treg cells induced by TGF-β, and the data demonstrate a dichotomy in thegeneration of pathogenic (TH17) T cells that induce autoimmunity and regulatory (Foxp3+) T Cells that inhibit autoimmune tissue injury.
Journal ArticleDOI
Naturally arising Foxp3-expressing CD25+CD4+ regulatory T cells in immunological tolerance to self and non-self.
TL;DR: Naturally arising CD25+CD4+ regulatory T cells actively maintain immunological self-tolerance, and are a good target for designing ways to induce or abrogate immunological tolerance to self and non-self antigens.
Journal ArticleDOI
Intraepithelial CD8+ tumor-infiltrating lymphocytes and a high CD8+/regulatory T cell ratio are associated with favorable prognosis in ovarian cancer
Eiichi Sato,Sara H. Olson,Jiyoung Ahn,Brian N. Bundy,Hiroyoshi Nishikawa,Feng Qian,Achim A. Jungbluth,Denise Frosina,Sacha Gnjatic,Christine B. Ambrosone,James L. Kepner,Tosin Odunsi,Gerd Ritter,Shashikant Lele,Yao-Tseng Chen,Haruo Ohtani,Lloyd J. Old,Kunle Odunsi +17 more
TL;DR: It is concluded that intraepithelial CD8+ TILs and a high CD8-/Treg ratio are associated with favorable prognosis in epithelial ovarian cancer.
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Transforming growth factor-beta regulation of immune responses.
TL;DR: This review highlights the findings that have advanced the understanding of TGF-beta in the immune system and in disease.
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A function for interleukin 2 in Foxp3-expressing regulatory T cells
Jason D. Fontenot,Jason D. Fontenot,Jeffrey P. Rasmussen,Marc A. Gavin,Alexander Y. Rudensky +4 more
TL;DR: Gene expression analysis showed that IL-2 signaling was required for maintenance of the expression of genes involved in the regulation of cell growth and metabolism, which seems to be critically required for maintaining the homeostasis and competitive fitness of Treg cells in vivo.
References
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Journal ArticleDOI
Suppressor Effector Function of CD4+CD25+ Immunoregulatory T Cells Is Antigen Nonspecific
TL;DR: Detailed characterization of the CD4+CD25+ population demonstrated that they do not contain memory or activated T cells and that they act through an APC-independent mechanism, demonstrating that their suppressor effector function is completely nonspecific.
Journal ArticleDOI
Regulatory T cells in autoimmmunity
TL;DR: Clonal deletion of autoreactive T cells in the thymus is not the sole mechanism for the induction of tolerance to self-antigens since partial depletion of peripheral CD4(+) T cells from neonatal and adult animals results in the development of organ-specific autoimmunity.
Journal ArticleDOI
Regulatory T cells in transplantation tolerance.
Kathryn J. Wood,Shimon Sakaguchi +1 more
TL;DR: The origin, allorecognition properties and molecular basis for the suppressive activity of CD4+CD25+ TReg cells, as well as their relationship to other populations of regulatory cells that exist after transplantation, remain a matter of debate.
Journal ArticleDOI
Natural versus adaptive regulatory T cells.
TL;DR: In this article, the existence of two subsets of CD4+ T(Reg) cells, natural and adaptive, was shown to differ in terms of their development, specificity, mechanism of action and dependence on T-cell receptor and co-stimulatory signalling.
Journal Article
Thymus and Autoimmunity: Production of CD25+CD4+ Naturally Anergic and Suppressive T Cells as a Key Function of the Thymus in Maintaining Immunologic Self-Tolerance
Misako Itoh,Takeshi Takahashi,Noriko Sakaguchi,Yuhshi Kuniyasu,Jun Shimizu,Fujio Otsuka,Shimon Sakaguchi +6 more
TL;DR: Results taken together indicate that anergic/suppressive CD25+4+8- thymocytes and peripheral T cells in normal naive mice may constitute a common T cell lineage functionally and developmentally distinct from other T cells, and that production of this unique immunoregulatory T cell population can be another key function of the thymus in maintaining immunologic self-tolerance.