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J Immunol. 2012 May 1;188(9):4369-75. doi: 10.4049/jimmunol.1102698. Epub 2012 Mar 28.

TGF-β converts apoptotic stimuli into the signal for Th9 differentiation.

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1
Department of Microbiology and Immunology, Stritch School of Medicine, Loyola University Chicago, Maywood, IL 60153, USA.

Abstract

Naturally arising CD4(+)CD25(+)FoxP3(+) regulatory T cells (nTregs) have an essential role in maintenance of immune homeostasis and peripheral tolerance. Previously, we reported that conventional CD4(+) and CD8(+) T cells undergo p53-induced CD28-dependent apoptosis (PICA) when stimulated with a combination of immobilized anti-CD3 and anti-CD28 Abs, whereas nTregs expand robustly under the same conditions, suggesting that there is a differential survival mechanism against PICA between conventional T cells and nTregs. In this study, we demonstrate that TGF-β signaling is required for nTregs to survive PICA. Conversely, when an active form of exogenous TGF-β is present, conventional T cells become resistant to PICA and undergo robust expansion instead of apoptosis, with reduction of the proapoptotic protein Bim and FoxO3a. A substantial fraction of PICA-resistant T cells expressed IL-9 (T(H)9 cells). Moreover, the presence of IL-6 along with TGF-β led to the generation of T(H)17 cells from conventional T cells. Together, the data demonstrate a novel role for TGF-β in the homeostasis of regulatory T cells and effector T cell differentiation and expansion.

PMID:
22461692
PMCID:
PMC3331903
DOI:
10.4049/jimmunol.1102698
[Indexed for MEDLINE]
Free PMC Article
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