Cited by 362T-cell and B-cell ImmunologyCancer, Hypoxia, and MetabolismMetabolism, Diabetes, and Cancer

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Glucose Availability Regulates IFN-γ Production and p70S6 Kinase Activation in CD8+ Effector T Cells

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Cham, Candace M, Gajewski, Thomas F·2005·The Journal of Immunology

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Abstract

Differentiation of CD8+ T cells from the naive to the effector state is accompanied by changes in basal gene expression profiles that parallel the acquisition of effector functions. Among these are metabolism genes, and we now show that 2C TCR transgenic effector CD8+ T cells express higher levels of glycolytic enzymes and display greater glucose uptake, a higher glycolytic rate, and increased lactate production compared with naive cells. To determine whether glucose was required for effector T cell functions, we regulated glucose availability in vitro. Glucose deprivation strongly inhibited IFN-γ gene expression, whereas IL-2 production was little affected. Inhibition correlated with diminished phosphorylation of p70S6 kinase and eIF4E binding protein 1 and a requirement for de novo protein synthesis, whereas other signaling pathways known to regulate IFN-γ expression were unaffected. Together, our data reveal that optimal induction of IFN-γ transcription is a glucose-dependent process, indicate that there are undefined factors that influence IFN-γ expression, and have implications for regulation of the effector phase of CD8+ T cell responses in tissue microenvironments.

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Authors: Cham, C. M., & Gajewski, T. F.
Affiliations: University of Chicago (US)
ORCID: Cham, Candace M
Gajewski, Thomas F
Venue: The Journal of Immunology
Publisher: Oxford University Press (OUP)
Published: 2005-04
Volume: 174
Issue: 8
Pages: 4670-4677
ISSN: 0022-1767 (ISSN-L)
1550-6606
DOI: 10.4049/jimmunol.174.8.4670
OpenAlex: W1853287186
Cited by: 359
References: 47
Citations by year: 2026: 11 · 2025: 28 · 2024: 32 · 2023: 32 · 2022: 29 · 2021: 28 · 2020: 34 · 2019: 21 · 2018: 21 · 2017: 18 · 2016: 18 · 2015: 14 · 2014: 18 · 2013: 9 · 2012: 13
FWCI: 1.89
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: academic.oup.com/pages/standard-publication-reuse-rights (vor)
Locations: The Journal of Immunology (publishedVersion)
PubMed (publishedVersion)
Funders: National Institute of Allergy and Infectious Diseases (R01AI047919, 1R01AI47919)
Topics: Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
Keywords: glucose availability, glucose deprivation, IFN-gamma production, p70 S6 kinase, CD8+ effector T cells, T cell metabolism, glycolysis, glucose uptake, lactic acid production, eIF4E-binding protein 1, de novo protein synthesis, interleukin-2, T cell differentiation
MeSH terms: Animals, Base Sequence, Carrier Proteins, Deoxyglucose, DNA, Enzyme Activation, Gene Expression Regulation, Glucose, Glycolysis, Interferon-gamma, Interleukin-2, Mice, Inbred C57BL, Mice, Inbred DBA, Mice, Transgenic, Phosphoproteins, Phosphorylation, RNA, Messenger, Signal Transduction, Up-Regulation, Mice, Knockout, CD8-Positive T-Lymphocytes, Cell Cycle Proteins, Ribosomal Protein S6 Kinases, 70-kDa, Eukaryotic Initiation Factors, Adaptor Proteins, Signal Transducing, Mice, In Vitro Techniques

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Glucose Availability Regulates IFN-γ Production and p70S6 Kinase Activation in CD8+ Effector T Cells

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