Cited by 1,035PI3K/AKT/mTOR signaling in cancerT-cell and B-cell ImmunologySignaling Pathways in Disease

Regulation and function of mTOR signalling in T cell fate decisions

Open access
Chi, Hongbo·2012·Nature Reviews Immunology

Abstract

The evolutionarily conserved kinase mTOR (mammalian target of rapamycin) couples cell growth and metabolism to environmental inputs in eukaryotes. T cells depend on mTOR signalling to integrate immune signals and metabolic cues for their proper maintenance and activation. Under steady-state conditions, mTOR is actively controlled by multiple inhibitory mechanisms, and this enforces normal T cell homeostasis. Antigen recognition by naive CD4(+) and CD8(+) T cells triggers mTOR activation, which in turn programmes the differentiation of these cells into functionally distinct lineages. This Review focuses on the signalling mechanisms of mTOR in T cell homeostatic and functional fates, and discusses the therapeutic implications of targeting mTOR in T cells.

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  • PI3K-AKT-mTOR signalling is essential for T cell activation and differentiation by upregulating metabolic programs and supporting their bioenergetic needs.

    “It is well established that PI3K–AKT–mTOR signalling is essential for T cell activation and differentiation by upregulating metabolic programs and supporting their bioenergetic needs46,47.”

    From Proteotoxic stress response drives T cell exhaustion and immune evasion (2025) · cites this paper as [46]

    In “Metabolism in T cell activation and differentiation” (page unavailable), the paper identifies PI3K–AKT as a central regulator of activation-induced metabolic reprogramming and says mTOR has a vital role in T-cell metabolic programmes. But “Sensing and propagating metabolic cues” (page unavailable) says the extent to which mTOR-dependent metabolism regulates differentiation remains contentious. The claim overstates that metabolic route as an established, essential basis for differentiation. (LLM, conf=0.86)

    Experimental — accuracy not yet measured
  • Rapamycin inhibition of mTOR boosts CD8+ T cell responses in preclinical studies.

    “inhibition of mTOR, a PI3K pathway intermediate, with rapamycin has been shown to stimulate CD8 + T cell responses in preclinical studies (110).”

    From Causes, consequences, and reversal of immune system aging (2013) · cites this paper as [110]

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Authors
Chi, H.
Affiliations
St. Jude Children's Research Hospital (US)
Corresponding author
Chi, Hongbo
Venue
Nature Reviews Immunology
Published
2012-04-20
Volume
12
Issue
5
Pages
325-338
ISSN
  • 1474-1733 (ISSN-L)
  • 1474-1741
OpenAlex
W2063888187
Cited by
1,035
References
154
Citations by year
2026: 70 · 2025: 89 · 2024: 90 · 2023: 103 · 2022: 96 · 2021: 94 · 2020: 82 · 2019: 51 · 2018: 62 · 2017: 77 · 2016: 60 · 2015: 57 · 2014: 39 · 2013: 49 · 2012: 16
FWCI
4.70
Type
journal article
Language
en
Open access
Locations
  • Nature reviews. Immunology (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • Cancer Research Institute
  • National Multiple Sclerosis Society
  • Lupus Research Institute
  • Lupus Research Alliance
  • American Lebanese Syrian Associated Charities
  • Multiple Sclerosis Society
  • National Institutes of Health
  • National Institute of Allergy and Infectious Diseases (R21AI094089)
  • National Institute of Neurological Disorders and Stroke (R01NS064599)
  • National Institute of Arthritis and Musculoskeletal and Skin Diseases (K01AR053573)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › PI3K/AKT/mTOR signaling in cancer
  • Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Signaling Pathways in Disease
Keywords
mTOR signaling, T cell fate determination, T cell homeostasis, T cell activation, T cell metabolism, T cell differentiation, CD4+ T cells, CD8+ T cells, mTOR inhibitors, immune checkpoint therapy, antigen recognition
MeSH terms
Animals, Humans, T-Lymphocytes, Signal Transduction, Cell Lineage, TOR Serine-Threonine Kinases

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