Publication Date:
2014-12-20
Description:
Immunological tolerance to self requires naturally occurring regulatory T (Treg) cells. Yet how they stably control autoimmune T cells remains obscure. Here, we show that Treg cells can render self-reactive human CD8(+) T cells anergic (i.e., hypoproliferative and cytokine hypoproducing upon antigen restimulation) in vitro, likely by controlling the costimulatory function of antigen-presenting cells. Anergic T cells were naive in phenotype, lower than activated T cells in T cell receptor affinity for cognate antigen, and expressed several coinhibitory molecules, including cytotoxic T lymphocyte-associated antigen-4 (CTLA-4). Using these criteria, we detected in healthy individuals anergic T cells reactive with a skin antigen targeted in the autoimmune disease vitiligo. Collectively, our results suggest that Treg cell-mediated induction of anergy in autoimmune T cells is important for maintaining self-tolerance.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Maeda, Yuka -- Nishikawa, Hiroyoshi -- Sugiyama, Daisuke -- Ha, Danbee -- Hamaguchi, Masahide -- Saito, Takuro -- Nishioka, Megumi -- Wing, James B -- Adeegbe, Dennis -- Katayama, Ichiro -- Sakaguchi, Shimon -- New York, N.Y. -- Science. 2014 Dec 19;346(6216):1536-40. doi: 10.1126/science.aaa1292.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Experimental Immunology, Immunology Frontier Research Center (IFReC-WPI), Osaka University, Osaka 565-0871, Japan. ; Experimental Immunology, Immunology Frontier Research Center (IFReC-WPI), Osaka University, Osaka 565-0871, Japan. shimon@ifrec.osaka-u.ac.jp nisihiro@ifrec.osaka-u.ac.jp. ; Experimental Immunology, Immunology Frontier Research Center (IFReC-WPI), Osaka University, Osaka 565-0871, Japan. Department of Dermatology, Graduate School of Medicine, Osaka University, Osaka565-0871, Japan. ; Department of Dermatology, Graduate School of Medicine, Osaka University, Osaka565-0871, Japan.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25525252" target="_blank"〉PubMed〈/a〉
Keywords:
Antigen-Presenting Cells/immunology
;
Autoimmune Diseases/*immunology
;
CD8-Positive T-Lymphocytes/*immunology
;
CTLA-4 Antigen
;
*Clonal Anergy
;
Humans
;
Lymphocyte Activation
;
Receptors, Antigen, T-Cell/immunology
;
*Self Tolerance
;
T-Lymphocytes, Regulatory/*immunology
;
Vitiligo/immunology
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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