TY - JOUR T1 - Detection of self-reactive CD8<sup>+</sup> T cells with an anergic phenotype in healthy individuals JF - Science JO - Science SP - 1536 LP - 1540 DO - 10.1126/science.aaa1292 VL - 346 IS - 6216 AU - Maeda, Yuka AU - Nishikawa, Hiroyoshi AU - Sugiyama, Daisuke AU - Ha, Danbee AU - Hamaguchi, Masahide AU - Saito, Takuro AU - Nishioka, Megumi AU - Wing, James B. AU - Adeegbe, Dennis AU - Katayama, Ichiro AU - Sakaguchi, Shimon Y1 - 2014/12/19 UR - http://science.sciencemag.org/content/346/6216/1536.abstract N2 - 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 naïve 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. For the immune system, balance is key. Immune cells must learn to eliminate invading pathogens but tolerate self. A cell type called regulatory T cells (Tregs) help to maintain this balance, but how they do so, particularly in humans, is unclear. Maeda et al. now report that Tregs “silence” T cells with modest reactivity to self. After culture with Tregs, the silenced T cells proliferated very little and produced almost no cytokines in response to antigen. The authors then examined T cells from healthy donors and from people with an autoimmune disease. Only healthy donors harbored silenced T cells, suggesting that if silencing goes awry, autoimmunity may result. Science, this issue p. 1536 ER -