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

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-? signaling is required for nTregs to survive PICA. Conversely, when an active form of exogenous TGF-? 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-? led to the generation of T(H)17 cells from conventional T cells. Together, the data demonstrate a novel role for TGF-? in the homeostasis of regulatory T cells and effector T cell differentiation and expansion.

SUBMITTER: Takami M 

PROVIDER: S-EPMC3331903 | biostudies-literature | 2012 May

REPOSITORIES: biostudies-literature