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

Qingsheng Li, Rajesh R. Rao, Koichi Araki, Kristen Pollizzi, Kunle Odunsi, Jonathan D. Powell, Protul A. Shrikant

Research output: Contribution to journalArticle

110 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)541-553
Number of pages13
JournalImmunity
Volume34
Issue number4
DOIs
StatePublished - Apr 22 2011

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

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    Li, Q., Rao, R. R., Araki, K., Pollizzi, K., Odunsi, K., Powell, J. D., & Shrikant, P. A. (2011). A Central Role for mTOR Kinase in Homeostatic Proliferation Induced CD8+ T Cell Memory and Tumor Immunity. Immunity, 34(4), 541-553. https://doi.org/10.1016/j.immuni.2011.04.006