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Journal ArticleDOI

Naturally Arising CD4+ Regulatory T Cells for Immunologic Self-Tolerance and Negative Control of Immune Responses

Shimon Sakaguchi
- 19 Mar 2004 - 
- Vol. 22, Iss: 1, pp 531-562
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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...

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Citations
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Directions in the immune targeting of cancer: lessons learned from the cancer-testis Ag NY-ESO-1.

TL;DR: The exceptional immunogenicity of this Ag coupled with its widespread distribution among many cancer types make it a very good vaccine candidate, with the potential to be used in vaccines against many types of malignancies.
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Reciprocal Expression of IL-35 and IL-10 Defines Two Distinct Effector Treg Subsets that Are Required for Maintenance of Immune Tolerance

TL;DR: It is demonstrated that IL-35-producing and IL-10-producing Tregs have a different activation status, do not share the same geographic locations in secondary lymphoid organs, and work in a complementary way to prevent autoimmunity.
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Regulatory T-lymphocytes in asthma

TL;DR: Two major and well-described CD4+ Treg cell subsets that are postulated to prevent immune responses against self-antigens and adaptive immune responses, respectively are focused on.
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CD40/CD40L interaction regulates CD4+CD25+ T reg homeostasis through dendritic cell-produced IL-2.

TL;DR: It is shown that naive T reg express low basal level of CD40L that is upregulated upon TCR‐triggered mediated activation that is persistently needed to assure T reg homeostasis, and four daily IL‐2 administrations to CD40KO mice normalize T reg number by promoting both their survival and homeostatic proliferation.
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Homeostasis of T cell numbers: from thymus production to peripheral compartmentalization and the indexation of regulatory T cells.

TL;DR: The sizes of the naïve and memory T cell compartments are governed by independent homeostatic mechanisms, which preserve the capacity to deal with any novel infection (conferred by the presence of naïve T cells) whilst ensuring the efficacy of memory responses when dealing with recurring antigens.
References
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Journal ArticleDOI

Control of Regulatory T Cell Development by the Transcription Factor Foxp3

TL;DR: Foxp3, which encodes a transcription factor that is genetically defective in an autoimmune and inflammatory syndrome in humans and mice, is specifically expressed in naturally arising CD4+ regulatory T cells and retroviral gene transfer of Foxp3 converts naïve T cells toward a regulatory T cell phenotype similar to that of naturally occurring CD4+.
Journal ArticleDOI

Innate Immune Recognition

TL;DR: Microbial recognition by Toll-like receptors helps to direct adaptive immune responses to antigens derived from microbial pathogens to distinguish infectious nonself from noninfectious self.
Journal ArticleDOI

Foxp3 programs the development and function of CD4 + CD25 + regulatory T cells

TL;DR: It is reported that the forkhead transcription factor Foxp3 is specifically expressed in CD4+CD25+ regulatory T cells and is required for their development and function and ectopic expression ofFoxp3 confers suppressor function on peripheral CD4-CD25− T cells.
Journal ArticleDOI

Immunologic self-tolerance maintained by activated T cells expressing IL-2 receptor alpha-chains (CD25). Breakdown of a single mechanism of self-tolerance causes various autoimmune diseases.

TL;DR: The authors showed that CD4+CD25+ cells contribute to maintaining self-tolerance by downregulating immune response to self and non-self Ags in an Ag-nonspecific manner, presumably at the T cell activation stage.
Journal ArticleDOI

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TL;DR: This unit discusses mammalian Toll receptors (TLR1‐10) that have an essential role in the innate immune recognition of microorganisms and are discussed are TLR‐mediated signaling pathways and antibodies that are available to detect specific TLRs.
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