Transforming Growth Factor-β Signaling Curbs Thymic Negative Selection Promoting Regulatory T Cell Development

被引：206
作者：
Ouyang, Weiming [1 ]
Beckett, Omar [1 ]
Ma, Qian [1 ]
Li, Ming O. [1 ]
机构：
[1] Mem Sloan Kettering Canc Ctr, Program Immunol, New York, NY 10065 USA
来源：
IMMUNITY | 2010年 / 32卷 / 05期
关键词：
TGF-BETA; CENTRAL TOLERANCE; IN-VIVO; FOXP3; EXPRESSION; SELF-PEPTIDE; APOPTOSIS; ANTIGEN; DIFFERENTIATION; HOMEOSTASIS; ACTIVATION;
D O I：
10.1016/j.immuni.2010.04.012
中图分类号：
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号：
100102 ;
摘要：
Thymus-derived naturally occurring regulatory T (nTreg) cells are necessary for immunological self-tolerance. nTreg cell development is instructed by the T cell receptor and can be induced by agonist antigens that trigger T cell-negative selection. How T cell deletion is regulated so that nTreg cells are generated is unclear. Here we showed that transforming growth factor-beta (TGF-beta) signaling protected nTreg cells and antigen-stimulated conventional T cells from apoptosis. Enhanced apoptosis of TGF-beta receptor-deficient nTreg cells was associated with high expression of proapoptotic proteins Bim, Box, and Bak and low expression of the antiapoptotic protein Bcl-2. Ablation of Bim in mice corrected the nTreg cell development and homeostasis defects. Our results suggest that nTreg cell commitment is independent of TGF-beta signaling. Instead, TGF-beta promotes nTreg cell survival by antagonizing T cell negative selection. These findings reveal a critical function for TGF-beta in control of autoreactive T cell fates with important implications for understanding T cell self-tolerance mechanisms.
引用
收藏
页码：642 / 653
页数：12
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