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Glucose Availability Regulates IFN-γ Production and p70S6 Kinase Activation in CD8+ Effector T Cells
Open accessAbstract
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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“It is known that the glycolytic metabolic pathway promotes IFN-γ expression and T cell effector function20,24–27.”
From Microbial short-chain fatty acids modulate CD8+ T cell responses and improve adoptive immunotherapy for cancer (2021) · cites this paper as [27]
In the citing paper
“Limiting glucose levels leads to cellular competition; this impairs T‐cell function via decreased mTOR signaling.”
From Tumor microenvironment signaling and therapeutics in cancer progression (2023) · cites this paper as [229]
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“Reduction in mTOR activity diminishes IFNγ transcripts in T cells, mitigating Th1 CD4+ T cell differentiation [227, 228, 229].”
From Tumor microenvironment signaling and therapeutics in cancer progression (2023) · cites this paper as [229]
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Cites
Schreiber, E. H., Matthias, P., Müller, M. M., & Schaffner, W. (1989) · Nucleic Acids Research · doi:10.1093/nar/17.15.6419 · Cited by 4,179
A Novel Transcription Factor, T-bet, Directs Th1 Lineage Commitment
Szabo, S. J., Kim, S. T., Costa, G. L., Zhang, X., Fathman, C. G., & Glimcher, L. H. (2000) · Cell · doi:10.1016/s0092-8674(00)80702-3 · Cited by 3,589
Uyttenhove, C., Pilotte, L., Théate, I., Stroobant, V., Colau, D., Parmentier, N., Boon, T., & Van den Eynde, B. J. (2003) · Nature Medicine · doi:10.1038/nm934 · Cited by 2,305
The CD28 Signaling Pathway Regulates Glucose Metabolism
Frauwirth, K. A., Riley, J. L., Harris, M. H., Parry, R. V., Rathmell, J. C., Plas, D. R., Elstrom, R. L., June, C. H., & Thompson, C. B. (2002) · Immunity · doi:10.1016/s1074-7613(02)00323-0 · Cited by 1,475 · cited 1×
“(23) reported that glucose use was induced by CD28 costimulation.”
BackgroundCD28 costimulation can promote T cell survival by enhancing the expression of Bcl-xL
Boise, L., Minn, A. J., Noel, P. J., June, C. H., Accavitti, M. A., Lindsten, T., & Thompson, C. B. (1995) · Immunity · doi:10.1016/1074-7613(95)90161-2 · Cited by 1,219
Frumento, G., Rotondo, R., Tonetti, M., Damonte, G., Benatti, U., & Ferrara, G. B. (2002) · The Journal of Experimental Medicine · doi:10.1084/jem.20020121 · Cited by 1,133
Control of Effector CD8 + T Cell Function by the Transcription Factor Eomesodermin
Pearce, E. L., Mullen, A. C., Martins, G. A., Krawczyk, C. M., Hutchins, A. S., Zediak, V. P., Banica, M., DiCioccio, C. B., Gross, D. A., Mao, C.-A., et al. (2003) · Science · doi:10.1126/science.1090148 · Cited by 1,014
Terness, P., Bauer, T. M., Röse, L., Dufter, C., Watzlik, A., Simon, H., & Opelz, G. (2002) · The Journal of Experimental Medicine · doi:10.1084/jem.20020052 · Cited by 965
Mammalian TOR: a homeostatic ATP sensor
Dennis, P. B., Jaeschke, A., Saitoh, M., Fowler, B., Kozma, S. C., & Thomas, G. (2001) · Science · doi:10.1126/science.1063518 · Cited by 962
Helper T Cell Differentiation Is Controlled by the Cell Cycle
Bird, J. J., Brown, D. R., Mullen, A. C., Moskowitz, N. H., Mahowald, M. A., Sider, J. R., Gajewski, T. F., Wang, C.-R., & Reiner, S. L. (1998) · Immunity · doi:10.1016/s1074-7613(00)80605-6 · Cited by 834
Self-citationLocalization of the primary metabolic block produced by 2-deoxyglucose
Wick, A. N., Drury, D. R., Nakada, H. I., Wolfe, J. B., Britton, B., & Grabowski, R. (1957) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)64988-9 · Cited by 780
Bierer, B. E., Mattila, P. S., Standaert, R. F., Herzenberg, L. A., Burakoff, S. J., Crabtree, G. R., & Schreiber, S. L. (1990) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.87.23.9231 · Cited by 706
BAD and glucokinase reside in a mitochondrial complex that integrates glycolysis and apoptosis
Danial, N. N., Gramm, C. F., Scorrano, L., Zhang, C.-Y., Krauss, S., Ranger, A. M., Robert Datta, S., Greenberg, M. E., Licklider, L. J., Lowell, B. B., et al. (2003) · Nature · doi:10.1038/nature01825 · Cited by 705
Modulation of Chromatin Structure Regulates Cytokine Gene Expression during T Cell Differentiation
Agarwal, S., & Rao, A. (1998) · Immunity · doi:10.1016/s1074-7613(00)80642-1 · Cited by 688
Alterations in Signal Transduction Molecules in T Lymphocytes from Tumor-Bearing Mice
Mizoguchi, H., O’Shea, J. J., Longo, D. L., Loeffler, C. M., McVicar, D. W., & Ochoa, A. C. (1992) · Science · doi:10.1126/science.1465616 · Cited by 632
Dumont, F. J., Staruch, M. J., Koprak, S., Melino, M. R., & SIGAL, N. H. (1990) · The Journal of Immunology · doi:10.4049/jimmunol.144.1.251 · Cited by 602
Regulation of T Cell Receptor CD3ζ Chain Expression byl-Arginine
Rodrı́guez, P. C., Zea, A. H., Culotta, K. S., Zabaleta, J., Ochoa, J. B., & Ochoa, A. C. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m110675200 · Cited by 537
Growth factors can influence cell growth and survival through effects on glucose metabolism
Vander Heiden, M. G., Plas, D. R., Rathmell, J. C., Fox, C. J., Harris, M. H., & Thompson, C. B. (2001) · Molecular and Cellular Biology · doi:10.1128/mcb.21.17.5899-5912.2001 · Cited by 536
l -Arginine Consumption by Macrophages Modulates the Expression of CD3ζ Chain in T Lymphocytes
Rodrı́guez, P. C., Zea, A. H., DeSalvo, J., Culotta, K. S., Zabaleta, J., Quiceno, D. G., Ochoa, J. B., & Ochoa, A. C. (2003) · The Journal of Immunology · doi:10.4049/jimmunol.171.3.1232 · Cited by 494
Rathmell, J. C., Heiden, M. G. V., Harris, M. H., Frauwirth, K. A., & Thompson, C. B. (2000) · Molecular Cell · doi:10.1016/s1097-2765(00)00066-6 · Cited by 467
Interferon‐γ expression by Th1 effector T cells mediated by the p38 MAP kinase signaling pathway
Rincón, M., Enslen, H., Raingeaud, J., Recht, M., Zapton, T., Su, M. S., Penix, L. A., Davis, R. J., & Flavell, R. A. (1998) · The EMBO Journal · doi:10.1093/emboj/17.10.2817 · Cited by 413
Yoshimoto, T., Okamura, H., Tagawa, Y., Iwakura, Y., & Nakanishi, K. (1997) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.94.8.3948 · Cited by 380
Indoleamine 2,3‐dioxygenase contributes to tumor cell evasion of T cell‐mediated rejection
Friberg, M., Jennings, R., Alsarraj, M., Dessureault, S., Cantor, A. B., Extermann, M., Mellor, A. L., Munn, D. H., & Antonia, S. J. (2002) · International Journal of Cancer · doi:10.1002/ijc.10645 · Cited by 374
Regulation of T Lymphocyte Metabolism
Frauwirth, K. A., & Thompson, C. B. (2004) · The Journal of Immunology · doi:10.4049/jimmunol.172.8.4661 · Cited by 371
Cells Expressing Indoleamine 2,3-Dioxygenase Inhibit T Cell Responses
Mellor, A. L., Keskin, D. B., Johnson, T. S., Chandler, P., & Munn, D. H. (2002) · The Journal of Immunology · doi:10.4049/jimmunol.168.8.3771 · Cited by 348
Hlx is induced by and genetically interacts with T-bet to promote heritable TH1 gene induction
Mullen, A. C., Hutchins, A. S., High, F. A., Lee, H. W., Sykes, K. J., Chodosh, L. A., & Reiner, S. L. (2002) · Nature Immunology · doi:10.1038/ni807 · Cited by 308
IL-18–stimulated GADD45β required in cytokine-induced, but not TCR-induced, IFN-γ production
Yang, J., Zhu, H., Murphy, T. L., Ouyang, W., & MURPHY, K. M. M. (2001) · Nature Immunology · doi:10.1038/84264 · Cited by 241
Penix, L. A., Sweetser, M. T., Weaver, W. M., Hoeffler, J. P., Kerppola, T. K., & Wilson, C. B. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.50.31964 · Cited by 195
Chakrabarti, R., Jung, C. Y., Lee, T. P., Liu, H., & Mookerjee, B. K. (1994) · The Journal of Immunology · doi:10.4049/jimmunol.152.6.2660 · Cited by 149
Lancki, D. W., Hsieh, C., & Fitch, F. W. (1991) · The Journal of Immunology · doi:10.4049/jimmunol.146.9.3242 · Cited by 107
Indoleamine 2,3-dioxygenase, immunosuppression and pregnancy
Mellor, A. L., Chandler, P., Lee, G. K., Johnson, T. S., Keskin, D. B., Lee, J. R., & Munn, D. H. (2002) · Journal of Reproductive Immunology · doi:10.1016/s0165-0378(02)00040-2 · Cited by 101
A translational rheostat for RFLAT-1 regulates RANTES expression in T lymphocytes
Nikolcheva, T., Pyronnet, S., Chou, S.-Y., Sonenberg, N., Song, A., Clayberger, C., & Krensky, A. M. (2002) · Journal of Clinical Investigation · doi:10.1172/jci15336 · Cited by 64
Lack of Effector Cell Function and Altered Tetramer Binding of Tumor-Infiltrating Lymphocytes
Blohm, U., Roth, E., Brommer, K., Dumrese, T., Rosenthal, F. M., & Pircher, H. (2002) · The Journal of Immunology · doi:10.4049/jimmunol.169.10.5522 · Cited by 64
Guilloux, Y., Viret, C., Gervois, N., Dréan, E. L., Pandolfino, M., Diez, E., & Jotereau, F. (1994) · European Journal of Immunology · doi:10.1002/eji.1830240905 · Cited by 60
The clinical value of 18F-FDG detection with a dual-head coincidence camera: a review
Ak, I., Blokland, J. A. K., Pauwels, E. J., & Stokkel, M. P. M. (2001) · European Journal of Nuclear Medicine and Molecular Imaging · doi:10.1007/s002590100501 · Cited by 51
Soutto, M., Zhou, W., & Aune, T. M. (2002) · The Journal of Immunology · doi:10.4049/jimmunol.169.12.6664 · Cited by 51
A translational rheostat for RFLAT-1 regulates RANTES expression in T lymphocytes
Nikolcheva, T., Pyronnet, S., Chou, S.-Y., Sonenberg, N., Song, A., Clayberger, C., & Krensky, A. M. (2002) · Journal of Clinical Investigation · doi:10.1172/jci0215336 · Cited by 49
A Minimal IFN-γ Promoter Confers Th1 Selective Expression
Soutto, M., Zhang, F., Enerson, B., Tong, Y., Boothby, M. R., & Aune, T. M. (2002) · The Journal of Immunology · doi:10.4049/jimmunol.169.8.4205 · Cited by 45
Unexpected Characteristics of the IFN-γ Reporters in Nontransformed T Cells
Zhu, H., Yang, J., Murphy, T. L., Ouyang, W., Wagner, F. H., Saparov, A., Weaver, C. T., & MURPHY, K. M. M. (2001) · The Journal of Immunology · doi:10.4049/jimmunol.167.2.855 · Cited by 45
2-Deoxy-D-glucose and insulin modify release of norepinephrine from rat hypothalamus
McCaleb, M. L., & Myers, R. D. (1982) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.1982.242.5.r596 · Cited by 38
Pascoe, W. S., Smythe, G. A., & Storlien, L. H. (1989) · Brain Research · doi:10.1016/0006-8993(89)90111-x · Cited by 30
Cham, C. M., Xu, H., O’Keefe, J. P., Rivas, F. V., Zagouras, P., & Gajewski, T. F. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m212741200 · Cited by 30
Self-citationRoussel, E., Gingras, M., Grimm, E. A., & Roth, J. A. (1995) · Cancer Immunology Immunotherapy · doi:10.1007/bf01788953 · Cited by 18
Effects of glucoprivation on gastric motility and pituitary oxytocin secretion in rats
Cato, R. K., Flanagan, L. M., Verbalis, J. G., & Stricker, E. M. (1990) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.1990.259.3.r447 · Cited by 17
MILLER, E., BATES, R., Koebel, D. A., FUCHS, B., & Sonnenfeld, G. (1998) · Physiology & Behavior · doi:10.1016/s0031-9384(98)00199-1 · Cited by 11
Requirements for activation of CD8+Murine T cells
Cronin, D. C., Lancki, D. W., & Fitch, F. W. (1994) · Immunologic Research · doi:10.1007/bf02935614 · Cited by 11
Effects of 2-Deoxy-D-Glucose Administration on Cytokine Production in BDF 1 Mice
Dréau, D., Morton, D. S., Foster, M., Fowler, N., & Sonnenfeld, G. (2000) · Journal of Interferon & Cytokine Research · doi:10.1089/107999000312667 · Cited by 8
Flagged first, then by citations
Research works printed but not linked: 46
- 1994, Immunol. Res., 215
- 1998, Immunity, 229
- 1998, Immunity, 765
- 2002, J. Biol. Chem., 21123
- 2002, J. Immunol., 3771
- 2003, J. Immunol., 1232
- 2002, Int. J. Cancer, 151
- 2003, Nat. Med., 1269
- 2004, J. Immunol., 4661
- 2003, Nature, 952
- 2001, Mol. Cell. Biol., 5899
- 2000, Mol. Cell, 683
- 2001, Eur. J. Nucl. Med., 763
- 2003, J. Biol. Chem., 17044
- 1989, Nucleic Acids Res., 6419
- 1957, J. Biol. Chem., 963
- 1991, J. Immunol., 3242
- 1997, Proc. Natl. Acad. Sci. USA, 3948
- 2001, Nat. Immunol., 157
- 1998, EMBO J., 2817
- 1996, J. Biol. Chem., 31964
- 2001, Science, 1102
- 2002, Immunity, 769
- 1995, Immunity, 87
- 1994, J. Immunol., 2660
- 1989, Brain Res., 23
- 1990, Am. J. Physiol., R447
- 1982, Am. J. Physiol., R596
- 2000, J. Interferon Cytokine Res., 247
- 1998, Physiol. Behav., 535
- 2002, J. Immunol., 4205
- 2001, J. Immunol., 855
- 2002, J. Immunol., 6664
- 2000, Cell, 655
- 2003, Science, 1041
- 2002, Nat. Immunol., 652
- 1990, Proc. Natl. Acad. Sci. USA, 9231
- 1990, J. Immunol., 251
- 2002, J. Clin. Invest., 119
- 1995, Cancer Immunol. Immunother., 1
- 1994, Eur. J. Immunol., 1966
- 2002, J. Immunol., 5522
- 2002, J Reprod. Immunol., 143
- 2002, J. Exp. Med., 447
- 2002, J. Exp. Med., 459
- 1992, Science, 1795
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Metadata
- Authors
- Cham, C. M., & Gajewski, T. F.
- Affiliations
- University of Chicago (US)
- 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
- 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
- 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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