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

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

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)
Venue
The Journal of Immunology
Published
2005-04
Volume
174
Issue
8
Pages
4670-4677
ISSN
  • 0022-1767 (ISSN-L)
  • 1550-6606
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
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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