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

ABSTRACT: T cell-specific deletion of the receptor for transforming growth factor-? (TGF-?) 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-? 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-?-unresponsive T cells underwent much more proliferation and differentiation into effector cells and induced lymphoproliferative disease. We propose that TGF-? signaling controls the self-reactivity of peripheral T cells but that in the absence of TGF-? signals, an added trigger such as lymphopenia is needed to drive overt autoimmune disease.

SUBMITTER: Zhang N

PROVIDER: S-EPMC3380154 | biostudies-literature | 2012 May

REPOSITORIES: biostudies-literature

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

Zhang Nu N Bevan Michael J MJ

Nature immunology 20120527 7

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. ...[more]

PMID: 22634866

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