Transforming Growth Factor-Beta Controls Development, Homeostasis, and Tolerance of T Cells by Regulatory T Cell-Dependent and -Independent Mechanisms

Immunity. 2006 Sep;25(3):455-71. doi: 10.1016/j.immuni.2006.07.011.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation / genetics
  • Cell Differentiation / immunology*
  • Cells, Cultured
  • Homeostasis / genetics
  • Homeostasis / immunology*
  • Immune Tolerance* / genetics
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mice, Transgenic
  • Signal Transduction / genetics
  • Signal Transduction / immunology
  • T-Lymphocytes / cytology
  • T-Lymphocytes / immunology
  • T-Lymphocytes / metabolism*
  • T-Lymphocytes, Regulatory / immunology
  • Transforming Growth Factor beta / deficiency
  • Transforming Growth Factor beta / genetics
  • Transforming Growth Factor beta / physiology*

Substances

  • Transforming Growth Factor beta