Detection of self-reactive CD8+ T cells with an anergic phenotype in healthy individuals

See allHide authors and affiliations

Science  19 Dec 2014:
Vol. 346, Issue 6216, pp. 1536-1540
DOI: 10.1126/science.aaa1292

You are currently viewing the abstract.

View Full Text

Log in to view the full text

Log in through your institution

Log in through your institution


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, silence is golden

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

View Full Text

Stay Connected to Science