Cutting Edge: Self-Antigen Controls the Balance between Effector and Regulatory T Cells in Peripheral Tissues

Gratz, Iris K.; Rosenblum, Michael D.; Maurano, Megan M.; Paw, Jonathan S.; Truong, Hong-An; Marshak‐Rothstein, Ann; Abbas, Abul K.

doi:10.4049/jimmunol.1301777

Cited by 64 publications

(69 citation statements)

References 15 publications

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“…Additionally, memory Treg cells displayed a high-rate of homeostatic proliferation even after antigen withdrawal (59). The continued proliferation and thus maintenance of memory Treg cells may be a consequence of their not requiring many of the signals thought to be essential for the responses of effector T cells, such as Akt and mTOR and becoming relatively independent of TCR-signals after initial activation (172).…”

Section: Critical Issues In Treg Cell Biologymentioning

confidence: 99%

Organ-Specific and Memory Treg Cells: Specificity, Development, Function, and Maintenance

2014

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Foxp3+ regulatory T cells (Treg cells) are essential for establishing and maintaining self-tolerance, and also inhibit immune responses to innocuous environmental antigens. Imbalances and dysfunction in Treg cells lead to a variety of immune-mediated diseases, as deficits in Treg cell function contribute to the development autoimmune disease and pathological tissue damage, whereas overabundance of Treg cells can promote chronic infection and tumorigenesis. Recent studies have highlighted the fact that Treg cells themselves are a diverse collection of phenotypically and functionally specialized populations, with distinct developmental origins, antigen-specificities, tissue-tropisms, and homeostatic requirements. The signals directing the differentiation of these populations, their specificities and the mechanisms by which they combine to promote organ-specific and systemic tolerance, and how they embody the emerging property of regulatory memory are the focus of this review.

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Section: Critical Issues In Treg Cell Biologymentioning

confidence: 99%

Organ-Specific and Memory Treg Cells: Specificity, Development, Function, and Maintenance

2014

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“…Several studies have focused on two sets of signals-interleukin-2 (IL-2) and antigen itself [60,61]. Thus, IL-2 is required for the survival of Treg and for maintaining their functional activity by promoting expression of FOXP3 and mediators of suppression, particularly CTLA-4 [62].…”

Section: Treg Functionsmentioning

confidence: 99%

Physiology and Pathology of Immune Dysregulation: Regulatory T Cells and Anergy

Torres¹,

López-Casado²,

León³

et al. 2017

Physiology and Pathology of Immunology

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The immune system is responsible for the defense of the organism. It controls what is introduced into it and identifies it as self from non-self. The defensive mechanisms activated by the immune system are directed against pathological microbes and toxic or allergenic proteins, and it must avoid responses that produce excessive damage of self-tissues, inducing tolerance to avoid autoimmunity and other immunopathologies. Regulatory Tcells play an essential role in these active processes, using several distinct suppressive mechanisms. The immune dysregulatory diseases result from defects affecting regulatory T cell development and/or function, including the impact of essential genes mutations for Tregulatory cell functions and the associated autoimmune syndromes.

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“…Although dispensable for the persistence of memory T helper cells, T Reg cells (perhaps as a consequence of self-antigen recognition) seem to be constitutively activated and require interactions through their TCR and CD28 to maintain effector populations [66][67][68][69][70] . However, strong TCR stimulation of T Reg cells by an autoantigen that instigates autoimmune disease can transiently destabilize their FOXP3 expression 71 , whereas the chronic stimulation of autoreactive effector T cells may induce FOXP3 expression in these cells and promote immune tolerance 72 .…”

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confidence: 99%

Harnessing the plasticity of CD4+ T cells to treat immune-mediated disease

2016

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| CD4 + T cells differentiate and acquire distinct functions to combat specific pathogens but can also adapt their functions in response to changing circumstances. Although this phenotypic plasticity can be potentially deleterious, driving immune pathology, it also provides important benefits that have led to its evolutionary preservation. Here, we review CD4 + T cell plasticity by examining the molecular mechanisms that regulate it -from the extracellular cues that initiate and drive cells towards varying phenotypes, to the cytosolic signalling cascades that decipher these cues and transmit them into the cell and to the nucleus, where these signals imprint specific gene expression programmes. By understanding how this functional flexibility is achieved, we may open doors to new therapeutic approaches that harness this property of T cells.

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Cutting Edge: Self-Antigen Controls the Balance between Effector and Regulatory T Cells in Peripheral Tissues

Cited by 64 publications

References 15 publications

Organ-Specific and Memory Treg Cells: Specificity, Development, Function, and Maintenance

Organ-Specific and Memory Treg Cells: Specificity, Development, Function, and Maintenance

Physiology and Pathology of Immune Dysregulation: Regulatory T Cells and Anergy

Harnessing the plasticity of CD4+ T cells to treat immune-mediated disease

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