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

Nu Zhang, Michael J. Bevan

Research output: Contribution to journalArticle

94 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)667-673
Number of pages7
JournalNature Immunology
Volume13
Issue number7
DOIs
StatePublished - Jul 1 2012

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ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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