| First Author | Li Q | Year | 2011 |
| Journal | Immunity | Volume | 34 |
| Issue | 4 | Pages | 541-53 |
| PubMed ID | 21511183 | Mgi Jnum | J:171599 |
| Mgi Id | MGI:4950617 | Doi | 10.1016/j.immuni.2011.04.006 |
| Citation | Li Q, et al. (2011) A Central Role for mTOR Kinase in Homeostatic Proliferation Induced CD8(+) T Cell Memory and Tumor Immunity. Immunity 34(4):541-53 |
| abstractText | The cell-intrinsic mechanisms guiding naive CD8(+) T cells for clonal expansion and memory generation via homeostatic proliferation (HP) are unclear. Here, we have shown that HP of naive CD8(+) T cells requires IL-7-, but not IL-15-induced mTOR kinase activation. HP-induced mTOR enhances transcription factor T-bet for functional maturation and CD122 expression, which sensitizes for an IL-15-dependent memory transition by favoring transcription factor Eomesodermin over T-bet. Inhibition of mTOR blocks T-bet and CD122 expression but preserves memory in an IL-15-independent manner by promoting Eomesodermin expression. The ability of rapamycin to augment HP-induced memory was cell-intrinsic given that silencing mTOR in CD8(+) T cells generated identical outcomes. Strikingly, HP-induced CD8(+) T cell memory generated by IL-15-dependent or -independent mechanisms demonstrated identical tumor efficacy. These results indicate a central role for mTOR in HP-induced CD8(+) T cell responses and demonstrate the importance for CD8(+) memory in HP-induced tumor efficacy. |
