Journal
SCIENCE
Volume 346, Issue 6216, Pages 1536-1540Publisher
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/science.aaa1292
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Funding
- Ministry of Education, Culture, Sports, Science, and Technology of Japan [20002007, 26253030, 23300354, 26290054]
- Core Research for Evolutional Science and Technology (CREST) from Japan Science and Technology Agency
- Health and Labor Sciences Research Grants, Research on Applying Health Technology from the Ministry of Health, Labor, and Welfare, Japan [H24-Clinical Cancer Research-general-006]
- Cancer Research Institute CLIP grant
- Grants-in-Aid for Scientific Research [25860356, 20002007, 26290054, 26253030, 23300354] Funding Source: KAKEN
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Immunological tolerance to self requires naturally occurring regulatory T (T-reg) cells. Yet how they stably control autoimmune T cells remains obscure. Here, we show that T-reg 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 T-reg cell-mediated induction of anergy in autoimmune T cells is important for maintaining self-tolerance.
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