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

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

Author information

1
Department of Immunology and the Howard Hughes Medical Institute, University of Washington, Seattle, Washington, USA.

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.

PMID:
22634866
PMCID:
PMC3380154
DOI:
10.1038/ni.2319
[Indexed for MEDLINE]
Free PMC Article

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