| First Author | Takami M | Year | 2012 |
| Journal | J Immunol | Volume | 188 |
| Issue | 9 | Pages | 4369-75 |
| PubMed ID | 22461692 | Mgi Jnum | J:188456 |
| Mgi Id | MGI:5440568 | Doi | 10.4049/jimmunol.1102698 |
| Citation | Takami M, et al. (2012) TGF-beta converts apoptotic stimuli into the signal for Th9 differentiation. J Immunol 188(9):4369-75 |
| abstractText | 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-beta signaling is required for nTregs to survive PICA. Conversely, when an active form of exogenous TGF-beta 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-beta led to the generation of T(H)17 cells from conventional T cells. Together, the data demonstrate a novel role for TGF-beta in the homeostasis of regulatory T cells and effector T cell differentiation and expansion. |
