Thymic regulatory T cell niche size is dictated by limiting IL-2 from antigen-bearing dendritic cells and feedback competition

被引:85
作者
Weist, Brian M. [1 ]
Kurd, Nadia [1 ]
Boussier, Jeremy [2 ]
Chan, Shiao Wei [1 ]
Robey, Ellen A. [1 ]
机构
[1] Univ Calif Berkeley, Dept Mol & Cell Biol, Div Immunol & Pathogenesis, Berkeley, CA 94720 USA
[2] Ecole Normale Super, F-75231 Paris, France
基金
美国国家卫生研究院;
关键词
RECEPTOR; SELECTION; INTERLEUKIN-2; INDUCTION; SUBSETS; AUTOIMMUNITY; ACTIVATION; EXPRESSION; MEDULLA; GOVERN;
D O I
10.1038/ni.3171
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
071005 [微生物学]; 100108 [医学免疫学];
摘要
The thymic production of regulatory T cells (T-reg cells) requires interleukin 2 (IL-2) and agonist T cell antigen receptor (TCR) ligands and is controlled by competition for a limited developmental niche, but the thymic sources of IL-2 and the factors that limit access to the niche are poorly understood. Here we found that IL-2 produced by antigen-bearing dendritic cells (DCs) had a key role in T-reg cell development and that existing T-reg cells limited new development of T-reg cells by competing for IL-2. Our data suggest that antigen-presenting cells (APCs) that can provide both IL-2 and a TCR ligand constitute the thymic niche and that competition by existing T-reg cells for a limited supply of IL-2 provides negative feedback for new production of T-reg cells.
引用
收藏
页码:635 / +
页数:9
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