TGF-β signaling to T cells inhibits autoimmunity during lymphopenia-driven proliferation

Nat Immunol. 2012 May 27;13(7):667-73. doi: 10.1038/ni.2319.

Abstract

T cell-specific deletion of the receptor for transforming growth factor-β (TGF-β) mediated by Cre recombinase expressed early in T cell development leads to early-onset lethal autoimmune disease that cannot be controlled by regulatory T cells. However, when we deleted that receptor through the use of Cre driven by a promoter that is active much later in T cell development, adult mice in which most peripheral CD4(+) or CD8(+) T cells lacked the receptor for TGF-β showed no signs of autoimmunity. Because of their enhanced responses to weak stimulation of the T cell antigen receptor, when transferred into lymphopenic recipients, naive TGF-β-unresponsive T cells underwent much more proliferation and differentiation into effector cells and induced lymphoproliferative disease. We propose that TGF-β signaling controls the self-reactivity of peripheral T cells but that in the absence of TGF-β signals, an added trigger such as lymphopenia is needed to drive overt autoimmune disease.

Publication types

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

MeSH terms

  • Animals
  • Autoimmunity / immunology*
  • Cell Proliferation*
  • Cells, Cultured
  • Female
  • Leukocyte Common Antigens / immunology
  • Lymphocyte Activation / immunology
  • Lymphopenia / immunology*
  • Lymphoproliferative Disorders / immunology
  • Male
  • Mice
  • Receptors, Antigen, T-Cell / immunology
  • Receptors, Transforming Growth Factor beta / genetics
  • Receptors, Transforming Growth Factor beta / immunology
  • Signal Transduction / immunology*
  • T-Lymphocytes / immunology*
  • Transforming Growth Factor beta / immunology*

Substances

  • Receptors, Antigen, T-Cell
  • Receptors, Transforming Growth Factor beta
  • Transforming Growth Factor beta
  • Leukocyte Common Antigens
  • Ptprc protein, mouse