期刊
IMMUNITY
卷 34, 期 4, 页码 541-553出版社
CELL PRESS
DOI: 10.1016/j.immuni.2011.04.006
关键词
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类别
资金
- National Institutes of Health [CA104645]
- Ovarian Cancer Research Fund
- Alliance Foundation of Roswell Park Cancer Institute
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.
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