Transforming growth factor-beta controls development, homeostasis, and tolerance of T cells by regulatory T cell-dependent and -independent mechanisms - PubMed (original) (raw)

Transforming growth factor-beta controls development, homeostasis, and tolerance of T cells by regulatory T cell-dependent and -independent mechanisms

Ming O Li et al. Immunity. 2006 Sep.

Free article

Abstract

The role of transforming growth factor-beta (TGF-beta) in inhibiting T cell functions has been studied with dominant-negative TGF-beta receptor transgenic models; however, the full impact of TGF-beta signaling on T cells and the mechanisms by which TGF-beta signals remain poorly understood. Here we show that mice with T cell-specific deletion of TGF-beta receptor II developed lethal inflammation associated with T cell activation and differentiation. In addition, TGF-beta signaling positively regulated T cell development and homeostasis. Development of CD8+ T cells and NKT cells, maintenance of peripheral Foxp3-expressing regulatory T cells, and survival of CD4+ T cells all depended on TGF-beta signaling. Both T helper 1 (Th1) differentiation and survival of activated CD4+ T cells required T-bet, the TGF-beta-regulated transcription factor, which controlled CD122 expression and IL-15 signaling in Th1 cells. This study reveals pleiotropic functions of TGF-beta signaling in T cells that may ensure a diverse and self-tolerant T cell repertoire in vivo.

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Comment in

Transforming growth factor-beta: taking control of T cells' life and death.
Horwitz DA. Horwitz DA. Immunity. 2006 Sep;25(3):399-401. doi: 10.1016/j.immuni.2006.08.013. Immunity. 2006. PMID: 16979574

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Transforming growth factor-beta controls development, homeostasis, and tolerance of T cells by regulatory T cell-dependent and -independent mechanisms - PubMed (original) (raw)