| First Author | Tinoco R | Year | 2009 |
| Journal | Immunity | Volume | 31 |
| Issue | 1 | Pages | 145-57 |
| PubMed ID | 19604493 | Mgi Jnum | J:151576 |
| Mgi Id | MGI:4354457 | Doi | 10.1016/j.immuni.2009.06.015 |
| Citation | Tinoco R, et al. (2009) Cell-intrinsic transforming growth factor-beta signaling mediates virus-specific CD8+ T cell deletion and viral persistence in vivo. Immunity 31(1):145-57 |
| abstractText | Although deficient CD8(+) T cell responses have long been associated with chronic viral infections, the underlying mechanisms are still unclear. Here we report that sustained transforming growth factor-beta (TGF-beta) expression and phosphorylation of its signaling mediator, Smad-2, were distinctive features of virus-specific CD8(+) T cells during chronic versus acute viral infections in vivo. The result was TGF-beta-dependent apoptosis of virus-specific CD8(+) T cells that related to upregulation of the proapoptotic protein Bim during chronic infection. Moreover, selective attenuation of TGF-beta signaling in T cells increased the numbers and multiple functions of antiviral CD8(+) T cells and enabled rapid eradication of the persistence-prone virus and memory generation. Finally, we found that cell-intrinsic TGF-beta signaling was responsible for virus-specific-CD8(+) T cell apoptosis and decreased numbers but was not necessary for their functional exhaustion. Our findings reveal persisting TGF-beta-Smad signaling as a hallmark and key regulator of CD8(+) T cell responses during chronic viral infections in vivo. |
