Cited by 21T-cell and B-cell ImmunologyPI3K/AKT/mTOR signaling in cancerImmunotherapy and Immune Responses

mTOR signaling promotes a robust and continuous production of IFN‐γ by human memory CD8+ T cells and their proliferation

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Setoguchi, Ruka, Matsui, Yui, Mouri, Kousuke·2015·European Journal of Immunology

Abstract

Human CD8+ T cells are functionally heterogeneous and can be divided into phenotypically and functionally distinct subsets according to CCR7 and CD45RA expression levels. Among these, CCR7 low CD45RA low effector memory CD8+ T cells (Tem) and CCR7 low CD45RA high CD8+ T cells, which are designated as Temra and considered to be terminally differentiated cells, are Ag‐experienced T cells but show different functionalities. Here, we show that, while Tem proliferate vigorously and produce IFN‐γ persistently and robustly, Temra proliferate poorly and lose the ability to produce IFN‐γ over time after TCR stimulation. Temra showed impaired cell growth upon TCR stimulation, which was associated with defective activation of the mammalian target of rapamycin (mTOR) signaling. Furthermore, rapamycin, an inhibitor of mTOR signaling, interfered with the robust and continuous proliferation of and IFN‐γ production by Tem at later time points after TCR stimulation. Thus, these data collectively indicate that activation of mTOR signaling is required for the robust functions of Tem cells in humans and suggest that defective mTOR signaling in Temra contributes to their functional impairment.

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Crossref · 10.1002/eji.201445086

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Authors
Setoguchi, R., Matsui, Y., & Mouri, K.
Affiliations
Kyoto University (JP)
Corresponding author
Setoguchi, Ruka
Venue
European Journal of Immunology
Publisher
Wiley
Published
2015-01-02
Volume
45
Issue
3
Pages
893-902
ISSN
  • 0014-2980 (ISSN-L)
  • 1521-4141
OpenAlex
W1573179618
Cited by
21
References
34
Citations by year
2026: 3 · 2025: 2 · 2024: 3 · 2023: 2 · 2021: 2 · 2020: 4 · 2019: 1 · 2016: 4
FWCI
0.61
Type
journal article
Language
en
Open access
Locations
  • European Journal of Immunology (publishedVersion)
  • PubMed (publishedVersion)
Funders
Ministry of Education, Culture, Sports, Science and Technology of Japan
Topics
  • Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › PI3K/AKT/mTOR signaling in cancer
  • Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
Keywords
mTOR signaling, IFN-gamma production, CD8+ T cells, effector memory T cells, TEMRA cells, T cell proliferation, T cell receptor stimulation, rapamycin, CCR7, CD45RA, T cell differentiation
MeSH terms
Female, Humans, Immunologic Memory, Immunosuppressive Agents, Interferon-gamma, Male, Receptors, Antigen, T-Cell, Signal Transduction, Leukocyte Common Antigens, CD8-Positive T-Lymphocytes, Sirolimus, Cell Proliferation, Receptors, CCR7, TOR Serine-Threonine Kinases

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