期刊
IMMUNITY
卷 32, 期 5, 页码 642-653出版社
CELL PRESS
DOI: 10.1016/j.immuni.2010.04.012
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类别
资金
- NIAMS [KO1 AR053595]
- Arthritis Foundation
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.
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