A Central Role for mTOR Kinase in Homeostatic Proliferation Induced CD8(+) T Cell Memory and Tumor Immunity

作者：Li Qingsheng; Rao Rajesh R; Araki Koichi; Pollizzi Kristen; Odunsi Kunle; Powell Jonathan D; Shrikant Protul A^*

来源：Immunity, 2011, 34(4): 541-553.

DOI：10.1016/j.immuni.2011.04.006

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.

• 出版日期2011-4-22