T cell-produced transforming growth factor-beta1 controls T cell tolerance and regulates Th1- and Th17-cell differentiation

Immunity. 2007 May;26(5):579-91. doi: 10.1016/j.immuni.2007.03.014. Epub 2007 May 3.

Abstract

TGF-beta1 is a regulatory cytokine with a pleiotropic role in immune responses. TGF-beta1 is widely expressed in leukocytes and stromal cells. However, the functions of TGF-beta1 expressed by specific lineages of cells remain unknown in vivo. Here, we show that mice with a T cell-specific deletion of the Tgfb1 gene developed lethal immunopathology in multiple organs, and this development was associated with enhanced T cell proliferation, activation, and CD4+ T cell differentiation into T helper 1 (Th1) and Th2 cells. TGF-beta1 produced by Foxp3-expressing regulatory T cells was required to inhibit Th1-cell differentiation and inflammatory-bowel disease in a transfer model. In addition, T cell-produced TGF-beta1 promoted Th17-cell differentiation and was indispensable for the induction of experimental autoimmune encephalomyelitis. These findings reveal essential roles for T cell-produced TGF-beta1 in controlling differentiation of T helper cells and controlling inflammatory diseases.

Publication types

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

MeSH terms

  • Animals
  • Cell Differentiation / immunology*
  • Cells, Cultured
  • Colitis / genetics
  • Colitis / immunology
  • Colitis / metabolism
  • Colitis / pathology
  • Encephalomyelitis, Autoimmune, Experimental / genetics
  • Encephalomyelitis, Autoimmune, Experimental / immunology
  • Encephalomyelitis, Autoimmune, Experimental / metabolism
  • Encephalomyelitis, Autoimmune, Experimental / pathology
  • Forkhead Transcription Factors / metabolism
  • Gene Deletion
  • Gene Expression Regulation
  • Homeostasis
  • Immune Tolerance / immunology*
  • Lymphocyte Activation / immunology
  • Mice
  • Mice, Knockout
  • T-Lymphocytes / cytology*
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / metabolism
  • Transforming Growth Factor beta1 / biosynthesis*
  • Transforming Growth Factor beta1 / genetics

Substances

  • Forkhead Transcription Factors
  • Foxp3 protein, mouse
  • Transforming Growth Factor beta1