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 Powell, Protul A. Shrikant

Research output: Contribution to journalArticle

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

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Interleukin-15
Immunity
Phosphotransferases
T-Lymphocytes
Neoplasms
Interleukin-7
Aptitude
Sirolimus
Transcription Factors

ASJC Scopus subject areas

  • Immunology and Allergy
  • Infectious Diseases
  • Immunology

Cite this

A Central Role for mTOR Kinase in Homeostatic Proliferation Induced CD8+ T Cell Memory and Tumor Immunity. / Li, Qingsheng; Rao, Rajesh R.; Araki, Koichi; Pollizzi, Kristen; Odunsi, Kunle; Powell, Jonathan; Shrikant, Protul A.

In: Immunity, Vol. 34, No. 4, 22.04.2011, p. 541-553.

Research output: Contribution to journalArticle

Li, Qingsheng ; Rao, Rajesh R. ; Araki, Koichi ; Pollizzi, Kristen ; Odunsi, Kunle ; Powell, Jonathan ; Shrikant, Protul A. / A Central Role for mTOR Kinase in Homeostatic Proliferation Induced CD8+ T Cell Memory and Tumor Immunity. In: Immunity. 2011 ; Vol. 34, No. 4. pp. 541-553.
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