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

Publication Type:

Journal Article


Nature immunology, Volume 13, Issue 7, p.667-73 (2012)


Animals, Antigens, CD45, AUTOIMMUNITY, Cell Proliferation, Cells, Cultured, Comparative Medicine Core Facility, Consortium Authored Paper, Female, Flow Cytometry Core Facility, Lymphocyte Activation, Lymphopenia, Lymphoproliferative Disorders, Male, MICE, Receptors, Antigen, T-Cell, Receptors, Transforming Growth Factor beta, Signal Transduction, T-Lymphocytes, Transforming Growth Factor beta


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.