The role of physiological self-antigen in the acquisition and maintenance of regulatory T-cell function

The CD4+CD25+ regulatory T cells (Tregs) are efficient regulators of autoimmunity, but the mechanism remains elusive. We summarize recent data for the conclusion that disease‐specific Tregs respond to tissue antigens to maintain physiological tolerance and prevent autoimmunity. First, polyclonal Tre...

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Published in:Immunological reviews 2006-08, Vol.212 (1), p.170-184
Main Authors: Samy, Eileen T., Setiady, Yulius Y., Ohno, Katsuhiro, Pramoonjago, Patcharin, Sharp, Colin, Tung, Kenneth S. K.
Format: Article
Language:English
Subjects:
Animals
Autoantigens - physiology
Autoimmune Diseases - immunology
Autoimmune Diseases - therapy
autoimmune ovarian disease
experimental autoimmune prostatitis
Immunosuppression
Mice
regulatory T cells
Self Tolerance
T-Lymphocytes, Regulatory - immunology
T-Lymphocytes, Regulatory - transplantation
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container_start_page 170
container_title Immunological reviews
container_volume 212
creator Samy, Eileen T.
Setiady, Yulius Y.
Ohno, Katsuhiro
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Sharp, Colin
Tung, Kenneth S. K.
description The CD4+CD25+ regulatory T cells (Tregs) are efficient regulators of autoimmunity, but the mechanism remains elusive. We summarize recent data for the conclusion that disease‐specific Tregs respond to tissue antigens to maintain physiological tolerance and prevent autoimmunity. First, polyclonal Tregs from antigen‐positive donors suppress autoimmune ovarian disease (AOD) or experimental autoimmune prostatitis in day 3 thymectomized (d3tx) mice more efficiently than Tregs from antigen‐negative donors. Second, Tregs of antigen‐negative adult mice respond to cognate antigen in vivo and rapidly gain disease‐specific Treg function. Third, in d3tx female recipients devoid of neonatal ovarian antigens, only female Tregs suppressed AOD; the male Tregs gain AOD‐suppressing function by responding to the ovarian antigen in the recipients and mask the supremacy of female Tregs in AOD suppression. Fourth, when Tregs completely suppress AOD, the ovary‐draining lymph node is the only location with evidence of profound and persistent (but reversible) host T‐cell suppression. Fifth, from these nodes, highly potent AOD‐suppressing Tregs are retrievable. We conclude that self‐tolerance involves the continuous priming of Tregs by autoantigens, and in autoimmune disease suppression, the effector T‐cell response is continuously negated by potent disease‐specific Tregs that accumulate at the site of autoantigen presentation.
doi_str_mv 10.1111/j.0105-2896.2006.00404.x
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subjects Animals
Autoantigens - physiology
Autoimmune Diseases - immunology
Autoimmune Diseases - therapy
autoimmune ovarian disease
experimental autoimmune prostatitis
Immunosuppression
Mice
regulatory T cells
Self Tolerance
T-Lymphocytes, Regulatory - immunology
T-Lymphocytes, Regulatory - transplantation
title The role of physiological self-antigen in the acquisition and maintenance of regulatory T-cell function
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