Cited by 186T-cell and B-cell ImmunologyCancer, Hypoxia, and MetabolismImmune cells in cancer

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The metabolic life and times of a T‐cell

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Michalek, Ryan D., Rathmell, Jeffrey C.·2010·Immunological Reviews

DOI 10.1111/j.1600-065x.2010.00911.xPMC PMC2983473

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Abstract

Summary: The regulation of lymphocyte homeostasis is critical for the development and formation of productive immune responses. Cell numbers must be maintained to allow sufficient numbers of lymphocytes to combat foreign pathogens but prevent the accumulation of excess lymphocytes that may increase the risk of developing autoimmunity or neoplasia. Cell extrinsic growth factors are essential to maintain homeostasis and cell survival, and it has become increasingly apparent that a key mechanism of this control is through regulation of cell metabolism. The metabolic state of T cells can have profound influences on cell growth and survival and even differentiation. In particular, resting T cells utilize an energy efficient oxidative metabolism but shift to a highly glycolytic metabolism when stimulated to grow and proliferate by pathogen encounter. After antigen clearance, T cells must return to a more quiescent oxidative metabolism to support T‐cell memory. This review highlights how these metabolic changes may be intricately involved with both T‐cell growth and death in the control of homeostasis and immunity.

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IL-7 promotes Glut1 trafficking and glucose uptake via STAT5-mediated activation of Akt to support T-cell survival
Wofford, J. A., Wieman, H. L., Jacobs, S. R., Zhao, Y., & Rathmell, J. C. (2007) · Blood · doi:10.1182/blood-2007-06-096297 · Cited by 424 · cited 10×
“On the receptor, residue Tyr499 in the cytoplasmic domain is required for T-cell development (68, 69) and is necessary to activate both the Jak ⁄ signal transducer and activator of transcription 5 (STAT5) and PI3K ⁄ Akt pathways (7, 70).”
BackgroundInfluentialSelf-citation
THE CENTRAL EFFECTORS OF CELL DEATH IN THE IMMUNE SYSTEM
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Linear Differentiation of Cytotoxic Effectors into Memory T Lymphocytes
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Background
Antigen-presenting dendritic cells provide the reducing extracellular microenvironment required for T lymphocyte activation
Angelini, G., Gardella, S., Ardy, M., Ciriolo, M. R., Filomeni, G., Trapani, G. D., Clarke, F. M., Sitia, R., & Rubartelli, A. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.022630299 · Cited by 372 · cited 1×
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Regulation of T Lymphocyte Metabolism
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“Although most investigation has centered on the signal transduction pathways that promote transcriptional activation of effector and cell growth genes, it has become apparent that cell metabolism must also play a critical role in immunity to permit transcriptional programs of highly energetic processes of cell growth,…”
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The serine/threonine kinase Pim-2 is a transcriptionally regulated apoptotic inhibitor.Preprint
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Glucose Availability Regulates IFN-γ Production and p70S6 Kinase Activation in CD8+ Effector T Cells
Cham, C. M., & Gajewski, T. F. (2005) · The Journal of Immunology · doi:10.4049/jimmunol.174.8.4670 · Cited by 359 · cited 10×
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BackgroundInfluential
Revving the Engine: Signal Transduction Fuels T Cell Activation
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“In particular, T cells cannot uptake cystine and require the reductive activity of APCs to provide the oxidized form of cystine, cysteine, to allow intracellular transport of this essential amino acid (16, 93, 94).”
BackgroundInfluential
T cell costimulation by chemokine receptors
Molon, B., Gri, G., Bettella, M., Gómez‐Moutón, C., Lanzavecchia, A., Martínez‐A, C., Mañes, S., & Viola, A. (2005) · Nature Immunology · doi:10.1038/ni1191 · Cited by 343
Roles of 5′-AMP-activated protein kinase (AMPK) in mammalian glucose homoeostasis
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“TCR signals can also activate the adenosine monophosphate (AMP)-activated protein kinase (AMPK) (49), which can also promote glucose uptake and oxidation in a manner consistent with the metabolism of resting T cells (50, 51).”
BackgroundResult
The victorin‐induced mitochondrial permeability transition precedes cell shrinkage and biochemical markers of cell death, and shrinkage occurs without loss of membrane integrity
Curtis, M. J., & Wolpert, T. (2004) · The Plant Journal · doi:10.1111/j.1365-313x.2004.02040.x · Cited by 332
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Regulation of the energy sensor AMP-activated protein kinase by antigen receptor and Ca2+ in T lymphocytes
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BackgroundResultInfluential
Akt and Bcl-xL Promote Growth Factor-independent Survival through Distinct Effects on Mitochondrial Physiology
Plas, D. R., Talapatra, S., Edinger, A. L., Rathmell, J. C., & Thompson, C. B. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m010551200 · Cited by 308
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Glucose is essential for proliferation and the glycolytic enzyme induction that provokes a transition to glycolytic energy production.
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BackgroundInfluential
Deficiency in Bak and Bax perturbs thymic selection and lymphoid homeostasis
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Anergic T Cells Are Metabolically Anergic
Zheng, Y., Delgoffe, G. M., Meyer, C. F., Chan, W., & Powell, J. D. (2009) · The Journal of Immunology · doi:10.4049/jimmunol.0803510 · Cited by 289 · cited 1×
“In addition, failure to obtain sufficient nutrients may lead to T-cell anergy and an inability to respond to mitogenic signals (80).”
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Activation of GLUT1 by metabolic and osmotic stress: potential involvement of AMP-activated protein kinase (AMPK)
Barnes, K., Ingram, J. C., Porras, O. H., Barros, L. F., Hudson, E. R., Fryer, L. G. D., Foufelle, F., Carling, D., Hardie, D. G., & Baldwin, S. A. (2002) · Journal of Cell Science · doi:10.1242/jcs.115.11.2433 · Cited by 289
Apoptosis Regulators Fas and Bim Cooperate in Shutdown of Chronic Immune Responses and Prevention of Autoimmunity
Hughes, P., Belz, G. T., Fortner, K. A., Budd, R. C., Strasser, A., & Bouillet, P. (2008) · Immunity · doi:10.1016/j.immuni.2007.12.017 · Cited by 271 · cited 1×
“(142) found a role for Fas and Bim following chronic MHV infection.”
Background
Homeostasis of αβ TCR+ T cells
Marrack, P., Bender, J., Hildeman, D. A., Jordan, M. B., Mitchell, T., Murakami, M., Sakamoto, A., Schaefer, B. C., Swanson, B., & Kappler, J. W. (2000) · Nature Immunology · doi:10.1038/77778 · Cited by 245
Cutaneous lymphoproliferation and lymphomas in interleukin 7 transgenic mice.
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“Conversely, transgenic overexpression of IL-7 can increase T-cell numbers, demonstrating that it is a limiting component of homeostatic regulation of T-cell survival (57, 58).”
Background
Shutdown of an acute T cell immune response to viral infection is mediated by the proapoptotic Bcl-2 homology 3-only protein Bim
Pellegrini, M., Belz, G. T., Bouillet, P., & Strasser, A. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2336198100 · Cited by 240 · cited 4×
“Indeed, resting T cells accumulate in Bim ⁄ ) animals (62, 63) and Bim ⁄ ) T cells can persist long-term following an immune response and accumulate as memory T cells (37, 125, 126).”
BackgroundInfluential
Puma cooperates with Bim, the rate-limiting BH3-only protein in cell death during lymphocyte development, in apoptosis induction
Erlacher, M., Labi, V., Manzl, C., Böck, G., Tzankov, A., Häcker, G. A., Michalak, E. M., Strasser, A., & Villunger, A. (2006) · The Journal of Experimental Medicine · doi:10.1084/jem.20061552 · Cited by 236 · cited 1×
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Distinct Roles of the Phosphatidylinositol 3-Kinase and STAT5 Pathways in IL-7-Mediated Development of Human Thymocyte Precursors
Pallard, C., Stegmann, A. P. A., van Kleffens, T., Smart, F. M., Venkitaraman, A. R., & Spits, H. (1999) · Immunity · doi:10.1016/s1074-7613(00)80052-7 · Cited by 203 · cited 2×
“Similarly, IL-7 signaling promotes Akt1 ⁄2 kinase activation, known regulators of glucose uptake and metabolism (70).”
Background
A novel inhibitor of glucose uptake sensitizes cells to FAS-induced cell death
Wood, T. E., Dalili, S., Simpson, C. D., Hurren, R., Mao, X., Suárez, F., Gronda, M., Eberhard, Y., Minden, M. D., Bilan, P. J., et al. (2008) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-08-0569 · Cited by 200 · cited 12×
“In addition, to death receptor-mediated influence over DCs and antigen presentation, decreased glucose metabolism in T cells after antigen clearance may also enhance T-cell sensitivity to death receptor signaling, as inhibition of glucose metabolism can lead to increased apoptosis in response to Fas (136, 143).”
BackgroundInfluential
Ceramide starves cells to death by downregulating nutrient transporter proteins
Guenther, G., Peralta, E. R., Rosales, K. R., Wong, S. Y., Siskind, L. J., & Edinger, A. L. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0802781105 · Cited by 199 · cited 1×
“RNAi of Glut1 in lymphoid cell lines can decrease proliferation and glucose limitation can cause cell cycle arrest or apoptosis (2, 85, 86).”
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Rapamycin-Mediated Enrichment of T Cells with Regulatory Activity in Stimulated CD4+ T Cell Cultures Is Not Due to the Selective Expansion of Naturally Occurring Regulatory T Cells but to the Induction of Regulatory Functions in Conventional CD4+ T Cells
Valmori, D., Tosello, V., Souleimanian, N. E., Godefroy, E., Scotto, L., Wang, Y., & Ayyoub, M. (2006) · The Journal of Immunology · doi:10.4049/jimmunol.177.2.944 · Cited by 196
Activated Akt promotes increased resting T cell size, CD28‐independent T cell growth, and development of autoimmunity and lymphoma
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“Conversely, metabolic excess may prevent apoptosis, exacerbate cell function, and potentially lead to inflammatory diseases (1, 4).”
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Glycogen Synthase Kinase 3α and 3β Mediate a Glucose-Sensitive Antiapoptotic Signaling Pathway To Stabilize Mcl-1
Zhao, Y., Altman, B. J., Coloff, J. L., Herman, C. E., Jacobs, S. R., Wieman, H. L., Wofford, J. A., DiMascio, L. N., Ilkayeva, O., Kelekar, A., et al. (2007) · Molecular and Cellular Biology · doi:10.1128/mcb.00153-07 · Cited by 195
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Apoptosis Regulators Bim and Fas Function Concurrently to Control Autoimmunity and CD8+ T Cell Contraction
Weant, A. E., Michalek, R. D., Khan, I. U., Holbrook, B. C., Willingham, M. C., & Grayson, J. M. (2008) · Immunity · doi:10.1016/j.immuni.2007.12.014 · Cited by 194 · cited 1×
“(141) found that compound mutants of Bim and Fas dramatically increased numbers of memory T-cell in the lymph node following an acute LCMV infection.”
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Observations on the Proliferation of Human Leucocytes Cultured with Phytohaemagglutinin
Cooper, E. H., Barkhan, P., & Hale, A. J. (1963) · British Journal of Haematology · doi:10.1111/j.1365-2141.1963.tb05446.x · Cited by 190 · cited 1×
“Although T-cell activation induces a rapid elevation in mitochondrial metabolism and oxygen consumption (15, 41), the most dramatic metabolic change is due to a sharp rise in glycolysis that results in a significant increase in the production of lactate (1, 9, 75, 76).”
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Generating intrathymic microenvironments to establish T-cell tolerance
Anderson, G., Lane, P. J. L., & Jenkinson, E. J. (2007) · Nature reviews. Immunology · doi:10.1038/nri2187 · Cited by 186 · cited 1×
“Upon entry into the peripheral pool of lymphocytes, the initial primary function of conventional T cells is surveillance (13, 14).”
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A mouse model for Glut-1 haploinsufficiency
Wang, D., Pascual, J. M., Yang, H., Engelstad, K., Mao, X., Cheng, J., Yoo, J. H., Noebels, J. L., & Vivo, D. C. D. (2006) · Human Molecular Genetics · doi:10.1093/hmg/ddl032 · Cited by 185 · cited 1×
“Glut1 knockout animals are early embryonic lethal (84), and conditional Glut1 knockouts have not yet been described.”
Background
IL-7 Is Essential for Homeostatic Control of T Cell Metabolism In Vivo
Jacobs, S. R., Michalek, R. D., & Rathmell, J. C. (2010) · The Journal of Immunology · doi:10.4049/jimmunol.0902593 · Cited by 183 · cited 1×
“have recently demonstrated that naive T cells are unable to maintain glycolysis in vivo in the absence of IL-7 (67).”
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The Noxa/Mcl-1 Axis Regulates Susceptibility to Apoptosis under Glucose Limitation in Dividing T Cells
Alves, N. L., Derks, I. A. M., Berk, E., Spijker, R., van Lier, R. A. W., & Eldering, E. (2006) · Immunity · doi:10.1016/j.immuni.2006.03.018 · Cited by 180 · cited 9×
“Multiple studies demonstrate that despite the presence of alternative metabolic fuels, limiting glucose metabolism in activated T cells results in decreased T-cell proliferation, deficient production of the effector cytokine interferon-c (IFNc), and the induction and activation of proapoptotic Bcl-2 family proteins su…”
BackgroundInfluential
Aerobic glycolysis and lymphocyte transformation
Hume, D. A., Radik, J., Ferber, E., & Weidemann, M. J. (1978) · Biochemical Journal · doi:10.1042/bj1740703 · Cited by 176 · cited 2×
“Although T-cell activation induces a rapid elevation in mitochondrial metabolism and oxygen consumption (15, 41), the most dramatic metabolic change is due to a sharp rise in glycolysis that results in a significant increase in the production of lactate (1, 9, 75, 76).”
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Numerical and functional deficiency in T helper cells in protein energy malnutrition.
Rk, C. (1983) · PubMed · Cited by 161
Glutamine Protects Activated Human T Cells from Apoptosis by Up-Regulating Glutathione and Bcl-2 Levels
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“The amino acid glutamine is also critical for T-cell metabolism and function, although as a mitochondrial fuel in addition to its role as an essential protein building block (98, 99).”
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Programming, demarcating, and manipulating CD8+ T‐cell memory
Badovinac, V. P., & Harty, J. T. (2006) · Immunological Reviews · doi:10.1111/j.0105-2896.2006.00384.x · Cited by 157 · cited 1×
“To restore immune homeostasis, approximately 90% of these effector cells undergo a process of apoptosis or programmed cell death (6, 34), which ensures that the lymphocyte pool remains diverse (112).”
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The adaptive response of the immune system to the particular malnutrition of eating disorders
Nova, E., Samartı́n, S., Gómez, S., Morandé, G., & Marcos, A. (2002) · European Journal of Clinical Nutrition · doi:10.1038/sj.ejcn.1601482 · Cited by 150 · cited 1×
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Signaling Takes a Breath – New Quantitative Perspectives on Bioenergetics and Signal Transduction
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“These physiologic processes have specific metabolic needs that are largely supplied by efficient generation of adenosine triphosphate (ATP) as an energy source and modest levels of biosynthetic precursors for cell maintenance (15).”
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Glycolysis inhibition sensitizes tumor cells to death receptors-induced apoptosis by AMP kinase activation leading to Mcl-1 block in translation
Pradelli, L. A., Bénéteau, M., Chauvin, C., Jacquin, M. A., Marchetti, S., Muñoz‐Pinedo, C., Auberger, P., Pende, M., & Ricci, J. (2009) · Oncogene · doi:10.1038/onc.2009.448 · Cited by 144 · cited 14×
“In addition, to death receptor-mediated influence over DCs and antigen presentation, decreased glucose metabolism in T cells after antigen clearance may also enhance T-cell sensitivity to death receptor signaling, as inhibition of glucose metabolism can lead to increased apoptosis in response to Fas (136, 143).”
BackgroundInfluential
Decreased Glucose Transporter Expression Triggers BAX-dependent Apoptosis in the Murine Blastocyst
Chi, M. M.-Y., Pingsterhaus, J. M., Carayannopoulos, M. O., & Moley, K. H. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.m005508200 · Cited by 142
Molecular mechanisms of lymphocyte extravasation. I. Studies of two selective inhibitors of lymphocyte recirculation.
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“When T cells are treated with pertussis toxin to block chemokine receptor signaling, they fail to migrate into normal periarteriolar T-cell zones in secondary lymphoid organs and are deprived signals normally present in these areas (43, 44).”
Background
Distinct Regions of the Interleukin-7 Receptor Regulate Different Bcl2 Family Members
Jiang, Q., Li, W., Hofmeister, R., Young, H. A., Hodge, D. R., Keller, J. R., Khaled, A. R., & Durum, S. K. (2004) · Molecular and Cellular Biology · doi:10.1128/mcb.24.14.6501-6513.2004 · Cited by 139 · cited 1×
“On the receptor, residue Tyr499 in the cytoplasmic domain is required for T-cell development (68, 69) and is necessary to activate both the Jak ⁄ signal transducer and activator of transcription 5 (STAT5) and PI3K ⁄ Akt pathways (7, 70).”
Background
Fas (CD95) participates in peripheral T cell deletion and associated apoptosis in vivo
Mogil, R. J., Radvanyi, L. G., González‐Quintial, R., Miller, R. G., Mills, G. B., Theofilopoulos, A. N., & Green, D. R. (1995) · International Immunology · doi:10.1093/intimm/7.9.1451 · Cited by 136 · cited 1×
“Although T-cell responses to peptide or Staphylococcus enterotoxin B (SEB) are abnormally enhanced and prolonged in Fas-deficient mice (140), the loss of Fas, tumor necrosis factor receptor 1 (TNFR1), or even both does not impede the death of T cells during shutdown of immune responses to acute HSV-1 infection (37).”
Background
Metabolic changes in activated T cells: An NMR study of human peripheral blood lymphocytes
Bental, M., & DEUTSCH, C. J. (1993) · Magnetic Resonance in Medicine · doi:10.1002/mrm.1910290307 · Cited by 136 · cited 1×
“largely subsist using mitochondrial oxidative metabolism of glucose and glutamine with the bulk of metabolic precursors fully oxidized for maximal ATP generation (16, 17).”
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Rab7 Prevents Growth Factor-Independent Survival by Inhibiting Cell-Autonomous Nutrient Transporter Expression
Edinger, A. L., Cinalli, R. M., & Thompson, C. B. (2003) · Developmental Cell · doi:10.1016/s1534-5807(03)00291-0 · Cited by 129 · cited 2×
“ing T cells from utilizing extracellular glucose as a fuel (73, 88, 89).”
Background
Loss of Bim Increases T Cell Production and Function in Interleukin 7 Receptor–deficient Mice
Pellegrini, M., Bouillet, P., Robati, M., Belz, G. T., Davey, G. M., & Strasser, A. (2004) · The Journal of Experimental Medicine · doi:10.1084/jem.20041328 · Cited by 128 · cited 2×
“Indeed, resting T cells accumulate in Bim ⁄ ) animals (62, 63) and Bim ⁄ ) T cells can persist long-term following an immune response and accumulate as memory T cells (37, 125, 126).”
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Identification and Validation of the Mitochondrial F1F0-ATPase as the Molecular Target of the Immunomodulatory Benzodiazepine Bz-423
Johnson, K. M., Chen, X., Boitano, A. E., Swenson, L., Opipari, A. W., & Glick, G. D. (2005) · Chemistry & Biology · doi:10.1016/j.chembiol.2005.02.012 · Cited by 127
Early effects of phytohaemagglutinin on glucose metabolism of normal human lymphocytes
Hedeskov, C. J. (1968) · Biochemical Journal · doi:10.1042/bj1100373 · Cited by 123 · cited 1×
“stimulate increased glycolysis as an energy source (28, 29), provide fuel for the pentose phosphate pathways that produce pentose sugars required for nucleic acid synthesis and NADH for reducing power (30), and contribute to lipid synthesis (31).”
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T- and B-Cell Abnormalities in Systemic Lupus Erythematosus
Nagy, G., Koncz, Á., & Perl, A. (2005) · Critical Reviews in Immunology · doi:10.1615/critrevimmunol.v25.i2.30 · Cited by 123
Bim mediates apoptosis of CD127lo effector T cells and limits T cell memory
Wojciechowski, S., Jordan, M. B., Zhu, Y., White, J., Zajac, A. J., & Hildeman, D. A. (2006) · European Journal of Immunology · doi:10.1002/eji.200635897 · Cited by 120 · cited 1×
“Indeed, resting T cells accumulate in Bim ⁄ ) animals (62, 63) and Bim ⁄ ) T cells can persist long-term following an immune response and accumulate as memory T cells (37, 125, 126).”
Background
Glucose Metabolism Attenuates p53 and Puma-dependent Cell Death upon Growth Factor Deprivation
Zhao, Y., Coloff, J. L., Ferguson, E. C., Jacobs, S. R., Cui, K., & Rathmell, J. C. (2008) · Journal of Biological Chemistry · doi:10.1074/jbc.m803580200 · Cited by 115 · cited 19×
“Jeffers JR, et al. Puma is an essential mediator of p53-dependent and -independent apoptotic pathways.”
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The Requirement of Reversible Cysteine Sulfenic Acid Formation for T Cell Activation and Function
Michalek, R. D., Nelson, K. J., Holbrook, B. C., Yi, J. S., Stridiron, D., Daniel, L. W., Fetrow, J. S., King, S. B., Poole, L. B., & Grayson, J. M. (2007) · The Journal of Immunology · doi:10.4049/jimmunol.179.10.6456 · Cited by 112
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Superantigen and endotoxin synergize in the induction of lethal shock
Blank, C. A., Luz, A., Bendigs, S., Erdmann, A. A., Wagner, H., & Heeg, K. (1997) · European Journal of Immunology · doi:10.1002/eji.1830270405 · Cited by 111 · cited 2×
“A chief component of clonal contraction and generation of memory is the loss of antigenic and inflammatory signals after antigen or pathogen clearance (36).”
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Exploring regulatory mechanisms of CD8 + T cell contraction
Prlic, M., & Bevan, M. J. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0808997105 · Cited by 110 · cited 1×
“Indeed, resting T cells accumulate in Bim ⁄ ) animals (62, 63) and Bim ⁄ ) T cells can persist long-term following an immune response and accumulate as memory T cells (37, 125, 126).”
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mTOR: taking cues from the immune microenvironment
Delgoffe, G. M., & Powell, J. D. (2009) · Immunology · doi:10.1111/j.1365-2567.2009.03125.x · Cited by 110
Impaired CD8 T cell memory and CD4 T cell primary responses in IL-7Rα mutant mice
Osborne, L. C., Dhanji, S., Snow, J. W., Priatel, J. J., Ma, M. C., Miners, M. J., Teh, H., Goldsmith, M. A., & Abraham, N. B. (2007) · The Journal of Experimental Medicine · doi:10.1084/jem.20061871 · Cited by 107 · cited 1×
“On the receptor, residue Tyr499 in the cytoplasmic domain is required for T-cell development (68, 69) and is necessary to activate both the Jak ⁄ signal transducer and activator of transcription 5 (STAT5) and PI3K ⁄ Akt pathways (7, 70).”
Background
The Mitogen-Induced Increase in T Cell Size Involves PKC and NFAT Activation of Rel/NF-κB-Dependent c-myc Expression
Grumont, R. J., Lock, P., Mollinari, M., Shannon, F. M., Moore, A., & Gerondakis, S. (2004) · Immunity · doi:10.1016/j.immuni.2004.06.004 · Cited by 106
Differential contribution of Puma and Noxa in dual regulation of p53‐mediated apoptotic pathways
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“Like Puma, Noxa is a p53 transcriptional target and can efficiently induce apoptosis (135).”
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Bax Deficiency Partially Corrects Interleukin-7 Receptor α Deficiency
Khaled, A. R., Li, W., Huang, J., Fry, T. J., Khaled, A. S., Mackall, C. L., Muegge, K., Young, H. A., & Durum, S. K. (2002) · Immunity · doi:10.1016/s1074-7613(02)00450-8 · Cited by 97
Surviving the crash: Transitioning from effector to memory CD8+ T cell
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“To restore immune homeostasis, approximately 90% of these effector cells undergo a process of apoptosis or programmed cell death (6, 34), which ensures that the lymphocyte pool remains diverse (112).”
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Phytohaemagglutinin stimulation of rat thymus lymphocyte glycolysis
Culvenor, J. G., & Weidemann, M. J. (1976) · Biochimica et Biophysica Acta (BBA) - General Subjects · doi:10.1016/0304-4165(76)90005-2 · Cited by 88 · cited 1×
“stimulate increased glycolysis as an energy source (28, 29), provide fuel for the pentose phosphate pathways that produce pentose sugars required for nucleic acid synthesis and NADH for reducing power (30), and contribute to lipid synthesis (31).”
Background
Development of lymphocytes in interleukin 7‐transgenic mice
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“Furthermore, this glycolytic program is reminiscent of the metabolism of many cancer cells (77) and allows T cells to rapidly supply their energy needs and increased intracellular glucose levels support the pentose phosphate pathways, which produce pentose sugars required for nucleic acid synthesis and NADPH for reduc…”
Background
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Background
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BackgroundSelf-citation
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“The amino acid glutamine is also critical for T-cell metabolism and function, although as a mitochondrial fuel in addition to its role as an essential protein building block (98, 99).”
Background
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BackgroundSelf-citation
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“Local availability of metabolic fuel sources and metabolites such as glucose, amino acids, and fatty acids may also have a role in exhaustion (197, 198).”
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Background
Immunosenescence and Inflamm-Aging As Two Sides of the Same Coin: Friends or Foes?
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See all 186

Authors: Michalek, R. D., & Rathmell, J. C.
Affiliations: Duke Medical Center (US)
Corresponding author: Rathmell, Jeffrey C.
ORCID: Rathmell, Jeffrey C.
Venue: Immunological Reviews
Publisher: Wiley
Published: 2010-06-15
Volume: 236
Issue: 1
Pages: 190-202
ISSN: 0105-2896 (ISSN-L)
1600-065X
DOI: 10.1111/j.1600-065x.2010.00911.x
PMC: PMC2983473
OpenAlex: W1672445637
Cited by: 186
References: 147
Citations by year: 2026: 2 · 2025: 3 · 2024: 10 · 2023: 8 · 2022: 17 · 2021: 10 · 2020: 13 · 2019: 11 · 2018: 22 · 2017: 15 · 2016: 11 · 2015: 3 · 2014: 15 · 2013: 14 · 2012: 24
FWCI: 1.15
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: onlinelibrary.wiley.com/termsAndConditions#vor (vor)
Locations: Immunological Reviews (publishedVersion)
PubMed (publishedVersion)
Europe PMC (PubMed Central) (acceptedVersion)
PubMed Central (acceptedVersion)
Funders: National Cancer Institute (R01CA123350)
National Institute of Allergy and Infectious Diseases (R01AI063345)
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 › Immunology and Microbiology › Immunology › Immune cells in cancer
Keywords: T cell metabolism, lymphocyte homeostasis, oxidative phosphorylation, glycolysis, T cell quiescence, T cell proliferation, T cell differentiation, T cell memory, T cell death, cell survival, cell growth, autoimmunity, cancer
MeSH terms: Animals, Cell Survival, Homeostasis, Humans, Immunity, T-Lymphocytes, Time Factors, Apoptosis, Models, Immunological, Lymphocyte Count

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The metabolic life and times of a T‐cell

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