Gene interactions and pathways from curated databases and text-mining
Immunity 2011, PMID: 21511183

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 D; Shrikant, Protul A

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.

Diseases/Pathways annotated by Medline MESH: Disease Progression, Neoplasms
Document information provided by NCBI PubMed

Text Mining Data

mTOR → IL-15: " Here, we have shown that HP of naive CD8+ T cells requires IL-7-, but not IL-15 induced mTOR kinase activation "

Manually curated Databases

No curated data.