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The metabolic life and times of a T‐cell
Open accessAbstract
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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“there has been an increasing understanding of the central importance of metabolism in regulating T cell function [5, 106, 107].”
From Hypoxia and hypoxia-inducible factors as regulators of T cell development, differentiation, and function (2013) · cites this paper as [107]
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Cites
Danial, N. N., & Korsmeyer, S. J. (2004) · Cell · doi:10.1016/s0092-8674(04)00046-7 · Cited by 4,651
Restoring function in exhausted CD8 T cells during chronic viral infection
Barber, D. L., Wherry, E. J., Masopust, D., Zhu, B., Allison, J. P., Sharpe, A. H., Freeman, G. J., & Ahmed, R. (2005) · Nature · doi:10.1038/nature04444 · Cited by 4,057 · cited 1×
“For example, inhibitory costimulatory receptors, such as programmed death-1 (PD-1), have been shown to suppress T-cell growth and proliferation when chronically stimulated (102, 103).”
BackgroundZlotnik, A., & Yoshie, O. (2000) · Immunity · doi:10.1016/s1074-7613(00)80165-x · Cited by 3,923 · cited 1×
“Most critically, T cells rely on chemokine signals to provide migratory direction (42) and T-cell receptor (TCR) and interleukin-7 (IL-7) signals for survival (5, 40).”
BackgroundBCL-2 family members and the mitochondria in apoptosisPreprint
Gross, A., McDonnell, J. M., & Korsmeyer, S. J. (1999) · Genes & Development · doi:10.1101/gad.13.15.1899 · Cited by 3,642
On Respiratory Impairment in Cancer Cells
Warburg, O. H. (1956) · Science · doi:10.1126/science.124.3215.269 · Cited by 3,472
Lymphoproliferation disorder in mice explained by defects in Fas antigen that mediates apoptosis
Watanabe‐Fukunaga, R., Brannan, C., Copeland, N., Jenkins, N., & Nagata, S. (1992) · Nature · doi:10.1038/356314a0 · Cited by 3,153 · cited 1×
“Defects in Fas or its cognate ligand FasL in mice or humans cause T-cell hyperplasia and autoantibody production, which resemble systemic lupus erythematosus and can lead to significant morbidity and mortality (138, 139).”
BackgroundPD-1 expression on HIV-specific T cells is associated with T-cell exhaustion and disease progression
Day, C. L., Kaufmann, D. E., Kiepiela, P., Brown, J. A., Moodley, E. S., Reddy, S., Mackey, E. W., Miller, J. D., Leslie, A. J., DePierres, C., et al. (2006) · Nature · doi:10.1038/nature05115 · Cited by 2,680 · cited 1×
“For example, inhibitory costimulatory receptors, such as programmed death-1 (PD-1), have been shown to suppress T-cell growth and proliferation when chronically stimulated (102, 103).”
BackgroundPUMA, a Novel Proapoptotic Gene, Is Induced by p53
Nakano, K., & Vousden, K. H. (2001) · Molecular Cell · doi:10.1016/s1097-2765(01)00214-3 · Cited by 2,315 · cited 1×
“Puma is regulated largely at a transcriptional level, with the tumor suppressor p53 playing a major role (132, 133).”
BackgroundFeuerer, M., Herrero, L., Cipolletta, D., Naaz, A., Wong, J., Nayer, A., Lee, J., Goldfine, A. B., Benoist, C., Shoelson, S., et al. (2009) · Nature Medicine · doi:10.1038/nm.2002 · Cited by 2,145 · cited 1×
“It is intriguing, however, that Treg cells have recently been identified as enriched in lipid-rich adipose tissues (111), suggesting that alterations in cell metabolism and availability of alternate fuels may affect Treg generation and provide a possible metabolic means to suppress or modify immunity.”
BackgroundWise, D. R., DeBerardinis, R. J., Mancuso, A., Sayed, N., Zhang, X.-Y., Pfeiffer, H. K., Nissim, I., Daikhin, E., Yudkoff, M., McMahon, S. B., et al. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0810199105 · Cited by 2,001 · cited 1×
“may be particularly sensitive to inhibition of glutamine metabolism (100, 101), resulting in cell cycle arrest or death—an addiction to glutamine that may be potentially exploited as a metabolic means to immunosuppression.”
Background
Cited by
Sorted by citations
Human nutrition, the gut microbiome and the immune system
Kau, A. L., Ahern, P. P., Griffin, N. W., Goodman, A. L., & Gordon, J. I. (2011) · Nature · doi:10.1038/nature10213 · Cited by 2,588
CD8 T Cell Exhaustion During Chronic Viral Infection and Cancer
McLane, L. M., Abdel-Hakeem, M. S., & Wherry, E. J. (2019) · Annual Review of Immunology · doi:10.1146/annurev-immunol-041015-055318 · Cited by 2,054
“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).”
BackgroundTranscriptional control of effector and memory CD8+ T cell differentiation
Kaech, S. M., & Cui, W. (2012) · Nature Reviews Immunology · doi:10.1038/nri3307 · Cited by 1,628
The Science and Translation of Lactate Shuttle Theory
Brooks, G. A. (2018) · Cell Metabolism · doi:10.1016/j.cmet.2018.03.008 · Cited by 1,486
“On one hand, T cell activation increases glycolysis and lactate accumulation due to low cellular mitochondrial content (Michalek and Rathmell, 2010), but on the other hand, lactate accumulation in the TME opposes T cell lactate efflux, leading to decreased cytokine production and cytotoxic activity…”
BackgroundImmunosenescence and Inflamm-Aging As Two Sides of the Same Coin: Friends or Foes?
Fulop, T., Larbi, A., Dupuis, G., Le Page, A., Frost, E. H., Cohen, A. A., Witkowski, J. M., & Franceschi, C. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2017.01960 · Cited by 1,364
Metabolic Regulation of T Lymphocytes
MacIver, N. J., Michalek, R. D., & Rathmell, J. C. (2013) · Annual Review of Immunology · doi:10.1146/annurev-immunol-032712-095956 · Cited by 1,244
“Upon recognition of cognate antigen in the presence of self-MHC and costimulatory signals, T cells grow, proliferate, and ultimately differentiate into distinct subsets that possess unique roles in maintaining functional responses and regulating immune homeostasis (82).”
BackgroundSelf-citationCD8+ T Cells: Foot Soldiers of the Immune System
Zhang, N., & Bevan, M. J. (2011) · Immunity · doi:10.1016/j.immuni.2011.07.010 · Cited by 1,157
“Recently, it has been demonstrated that in addition to costimulatory signals, such as CD28-induced PI-3K-Akt-mTOR signaling (Michalek and Rathmell, 2010), TCR-ERK signaling is required for enhanced glycolysis and glucose plus glutamine uptake (Carr et al., 2010; Marko et al., 2010).”
InfluentialRegulation and function of mTOR signalling in T cell fate decisions
Chi, H. (2012) · Nature Reviews Immunology · doi:10.1038/nri3198 · Cited by 1,035
Inhibiting glycolytic metabolism enhances CD8+ T cell memory and antitumor function
Sukumar, M., Liu, J., Ji, Y., Subramanian, M., Crompton, J. G., Yu, Z., Roychoudhuri, R., Palmer, D. C., Muranski, P., Karoly, E. D., et al. (2013) · Journal of Clinical Investigation · doi:10.1172/jci69589 · Cited by 952
Cancer Cell Metabolism: One Hallmark, Many Faces
Cantor, J. R., & Sabatini, D. M. (2012) · Cancer Discovery · doi:10.1158/2159-8290.cd-12-0345 · Cited by 989
“As mentioned above, cancer cells and normal proliferating cells share a similar collection of metabolic demands and adaptations (21, 30).”
BackgroundMetabolic targets for cancer therapy
Galluzzi, L., Kepp, O., Heiden, M. G. V., & Kroemer, G. (2013) · Nature Reviews Drug Discovery · doi:10.1038/nrd4145 · Cited by 731
The role of metabolism in the pathogenesis of osteoarthritis
Mobasheri, A., Rayman, M. P., Gualillo, O., Sellam, J., van der Kraan, P., & Fearon, U. (2017) · Nature Reviews Rheumatology · doi:10.1038/nrrheum.2017.50 · Cited by 742
San-Millán, I., & Brooks, G. A. (2016) · Carcinogenesis · doi:10.1093/carcin/bgw127 · Cited by 640
“When activated for cell growth and proliferation, T-cells switch to highly glycolytic activity (180) thus producing and exporting important amount of lactate through MCTs.”
BackgroundA two-way street: reciprocal regulation of metabolism and signalling
Wellen, K. E., & Thompson, C. B. (2012) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3305 · Cited by 528
Changes in Nutritional Status Impact Immune Cell Metabolism and Function
Alwarawrah, Y., Kiernan, K., & MacIver, N. J. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2018.01055 · Cited by 534
Cancer metabolism: current perspectives and future directions
Muñoz-Pinedo, C., El Mjiyad, N., & Ricci, J.-E. (2012) · Cell Death & Disease · doi:10.1038/cddis.2011.123 · Cited by 385
“during acute stimulation and cells exposed to growth factors.(4,5) Indeed, like cancer cells, these cells need to support high proliferation rates and thus require efficient”
BackgroundStaron, M. M., Gray, S. M., Marshall, H. D., Parish, I. A., Chen, J. H., Perry, C. J., Cui, G., Li, M. O., & Kaech, S. M. (2014) · Immunity · doi:10.1016/j.immuni.2014.10.013 · Cited by 402
“…receptors are of particular interest because they function in parallel pathways to control many aspects of T cell differentiation, proliferation, function, and survival (Finlay and Cantrell, 2011; Michalek and Rathmell, 2010; Pearce and Pearce, 2013; Powell and Delgoffe, 2010; Rao et al., 2010).”
BackgroundAcetate Promotes T Cell Effector Function during Glucose Restriction
Qiu, J., Villa, M., Sanin, D. E., Buck, M. D., O’Sullivan, D., Ching, R., Matsushita, M., Grzes, K. M., Winkler, F., Chang, C.-H., et al. (2019) · Cell Reports · doi:10.1016/j.celrep.2019.04.022 · Cited by 342
“T cells must acquire sufficient nutrients to engage the appropriate metabolism to support effector functions during infection and cancer (Buck et al., 2015, 2017; Buck et al., 2017; Chang et al., 2013; Michalek and Rathmell, 2010; O’Sullivan and Pearce, 2015; Pearce et al., 2013).”
BackgroundROS homeostasis and metabolism: a critical liaison for cancer therapy
Kim, J., Kim, J., & Bae, J. (2016) · Experimental & Molecular Medicine · doi:10.1038/emm.2016.119 · Cited by 304
IL-7 signaling and CD127 receptor regulation in the control of T cell homeostasis
Carrette, F., & Surh, C. D. (2012) · Seminars in Immunology · doi:10.1016/j.smim.2012.04.010 · Cited by 257
“Besides being dependent on balanced pro- and anti-apoptotic signals, resting T cell survival is also dependent on their ability to maintain cellular metabolism, and particularly glucose metabolism [64].”
BackgroundBile acids and intestinal microbiota in autoimmune cholestatic liver diseases
Li, Y., Tang, R., Leung, P. S. C., Gershwin, M. E., & Ma, X. (2017) · Autoimmunity Reviews · doi:10.1016/j.autrev.2017.07.002 · Cited by 247
Chen, D., Tang, T.-X., Deng, H., Yang, X., & Tang, Z. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.747324 · Cited by 250
“In addition to dependence on a dynamic balance of proapoptotic and anti-apoptotic signals, it should be emphasized that the capacity of IL-7 to maintain steady metabolism— especially glucose metabolism—is also critical for T-cell survival (28).”
BackgroundThe liver kinase B1 is a central regulator of T cell development, activation, and metabolism
MacIver, N. J., Blagih, J., Saucillo, D. C., Tonelli, L., Griss, T., Rathmell, J. C., & Jones, R. G. (2011) · The Journal of Immunology · doi:10.4049/jimmunol.1100367 · Cited by 235
Self-citationMcNamee, E. N., Korns Johnson, D., Homann, D., & Clambey, E. T. (2013) · Immunologic Research · doi:10.1007/s12026-012-8349-8 · Cited by 234
“In recent years, there has been an increasing understanding of the central importance of metabolism in regulating T cell function [5, 106, 107].”
BackgroundDichloroacetate and cancer: New home for an orphan drug?
Kankotia, S., & Stacpoole, P. W. (2014) · Biochimica et Biophysica Acta (BBA) - Reviews on Cancer · doi:10.1016/j.bbcan.2014.08.005 · Cited by 226
Qiao, G., Bucsek, M. J., Winder, N. M., Chen, M., Giridharan, T., Olejniczak, S. H., Hylander, B. L., & Repasky, E. A. (2018) · Cancer Immunology Immunotherapy · doi:10.1007/s00262-018-2243-8 · Cited by 213
Sugar-free approaches to cancer cell killing
Mjiyad, N. E., Caro‐Maldonado, A., Ramírez‐Peinado, S., & Muñoz‐Pinedo, C. (2010) · Oncogene · doi:10.1038/onc.2010.466 · Cited by 198
“A high rate of glucose utilization is not exclusive of tumor cells, and other highly proliferative cells such as T lymphocytes also switch to aerobic glycolysis when stimulated to proliferate (Michalek and Rathmell, 2010).”
BackgroundLian, G., Gnanaprakasam, J. R., Wang, T., Wu, R., Chen, X., Liu, L., Shen, Y., Yang, M., Yang, J. J. J., Chen, Y., et al. (2018) · eLife · doi:10.7554/elife.36158 · Cited by 199
Metabolic Stress in Autophagy and Cell Death PathwaysPreprint
Altman, B. J., & Rathmell, J. C. (2012) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a008763 · Cited by 204
Self-citationTumor Microenvironment: A Metabolic Player that Shapes the Immune Response
Cassim, S., & Pouysségur, J. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms21010157 · Cited by 192
“T cells switch to a program of anabolic growth and biomass accumulation, which by definition dictates increased demand for ATP and metabolic resources to generate daughter cells.”
BackgroundInfluentialMetabolic reprogramming and metabolic dependency in T cells
Wang, R., & Green, D. R. (2012) · Immunological Reviews · doi:10.1111/j.1600-065x.2012.01155.x · Cited by 180
“The active T cell must acquire metabolic support for converting available metabolic resources into biomass, producing sufficient adenosine triphosphate (ATP) as a source of free energy (for thermodynamically unfavorable cellular processes), and finally, generating metabolic products as signals for triggering intra and…”
BackgroundReinforce the antitumor activity of CD 8 + T cells via glutamine restriction
Nabe, S., Yamada, T., Suzuki, J., Toriyama, K., Yasuoka, T., Kuwahara, M., Shiraishi, A., Takenaka, K., Yasukawa, M., & Yamashita, M. (2018) · Cancer Science · doi:10.1111/cas.13827 · Cited by 179
Palmer, C. S., Ostrowski, M., Gouillou, M., Tsai, L. M., Yu, D., Zhou, J., Henstridge, D. C., Maisa, A., Hearps, A. C., Lewin, S. R., et al. (2013) · AIDS · doi:10.1097/qad.0000000000000128 · Cited by 176
“Given the sustained energy requirements of activated T cells (as reviewed in references [18] and [25]) we hypothesized that T cells would up-regulate Glut1 expression and increase glucose transport in the context of HIV infection.”
BackgroundEpstein, T., Xu, L., Gillies, R. J., & Gatenby, R. A. (2014) · Cancer & Metabolism · doi:10.1186/2049-3002-2-7 · Cited by 160
“Consistent with this, aerobic glycolysis is observed in numerous physiological processes that are associated with acute membrane events such as lymphocyte proliferation and antibody secretion [3,7], macrophages migration [8], embryonic cytokinesis and cell migration [4].”
Gemta, L. F., Siska, P. J., Nelson, M. E., Gao, X., Liu, X., Locasale, J. W., Yagita∥, H., Slingluff, C. L., Hoehn, K. L., Rathmell, J. C., et al. (2019) · Science Immunology · doi:10.1126/sciimmunol.aap9520 · Cited by 158
Self-citationKouidhi, S., Elgaaïed, A. B., & Chouaïb, S. (2017) · Frontiers in Immunology · doi:10.3389/fimmu.2017.00270 · Cited by 145
“To maintain a proper response, T-cell activation requires the upregulation of both glucose and amino acid transporters (1, 76).”
BackgroundRole of Polyamines in Immune Cell Functions
Hesterberg, R. S., Cleveland, J. L., & Epling‐Burnette, P. K. (2018) · Medical Sciences · doi:10.3390/medsci6010022 · Cited by 142
“Importantly, all of these cells must adjust their metabolic activity to meet functional demands that include migration, proliferation and sometimes long-lasting persistence in these diverse environments [5,6].”
BackgroundGlucose metabolism and metabolic flexibility in blood platelets
Aibibula, M., Naseem, K. M., & Sturmey, R. G. (2018) · Journal of Thrombosis and Haemostasis · doi:10.1111/jth.14274 · Cited by 132
“These data suggest that the functional responses were driven by choosing aerobic glycolysis over OXPHOS of glucose and glycogen consistent with a ‘Warburg’ or aerobic glycolytic phenotype (31,32).”
BackgroundtRNA-m1A modification promotes T cell expansion via efficient MYC protein synthesis
Liu, Y., Zhou, J., Li, X., Zhang, X., Shi, J., Wang, X., Li, H., Miao, S., He, X., He, X., et al. (2022) · Nature Immunology · doi:10.1038/s41590-022-01301-3 · Cited by 136
The RIG-I-like Receptor LGP2 Controls CD8+ T Cell Survival and Fitness
Suthar, M. S., Ramos, H. J., Brassil, M. M., Netland, J., Chappell, C. P., Blahnik, G., McMillan, A., Diamond, M., Clark, E. A., Bevan, M. J., et al. (2012) · Immunity · doi:10.1016/j.immuni.2012.07.004 · Cited by 127
“Both cell-intrinsic and -extrinsic apoptotic signaling pathways are important in regulating peripheral deletion of activated CD8+ T cells (Michalek and Rathmell, 2010).”
BackgroundDistinct metabolic programs in activated T cells: opportunities for selective immunomodulation
Wahl, D. R., Byersdorfer, C. A., Ferrara, J. L. M., Opipari, A. W., & Glick, G. D. (2012) · Immunological Reviews · doi:10.1111/j.1600-065x.2012.01148.x · Cited by 125
“More recent studies have observed a similar metabolic phenotype in unstimulated mouse and human T cells (7, 8), suggesting that the dependence on OXPHOS is a generalizable feature of resting lymphocyte populations (9).”
ResultModulation of T Cell Metabolism and Function through Calcium Signaling
Fracchia, K. M., Pai, C., & Walsh, C. M. (2013) · Frontiers in Immunology · doi:10.3389/fimmu.2013.00324 · Cited by 117
“Instead, it has been proposed that this switch is necessary to facilitate the rapid clonal expansion required to eliminate a microbial infection (45).”
BackgroundmTOR and metabolic pathways in T cell quiescence and functional activation
Yang, K., & Chi, H. (2012) · Seminars in Immunology · doi:10.1016/j.smim.2012.12.004 · Cited by 119
What Fuels Natural Killers? Metabolism and NK Cell Responses
Gardiner, C. M., & Finlay, D. K. (2017) · Frontiers in Immunology · doi:10.3389/fimmu.2017.00367 · Cited by 118
MYC in Regulating Immunity: Metabolism and Beyond
Gnanaprakasam, J. R., & Wang, R. (2017) · Genes · doi:10.3390/genes8030088 · Cited by 111
Ananieva, E. A., Patel, C. H., Drake, C. H., Powell, J. D., & Hutson, S. M. (2014) · Journal of Biological Chemistry · doi:10.1074/jbc.m114.554113 · Cited by 101
“These results are consistent with other reports (36) showing that during T cell activation, the T cells enhance utilization of amino acids to meet their increased metabolic, energy, and protein synthesis demands.”
BackgroundResultPiotrowski, J. T., Gomez, T. S., Schoon, R. A., Mangalam, A. K., & Billadeau, D. D. (2013) · Molecular and Cellular Biology · doi:10.1128/mcb.01288-12 · Cited by 101
“Finally, we investigated whether decreased GLUT1 on activated WASHout T cells affected glucose uptake since the primary form of metabolism in activated T cells is aerobic glycolysis (42), which is important for efficient T cell survival and proliferation (43, 44).”
BackgroundPrevite, D. M., O’Connor, E. C., Novak, E. A., Martins, C. P., Mollen, K. P., & Piganelli, J. D. (2017) · PLoS ONE · doi:10.1371/journal.pone.0175549 · Cited by 96
CD8 + T cell exhaustion in anti‐tumour immunity: The new insights for cancer immunotherapy
Huang, Y., Jia, A., Wang, Y., & Liu, G. (2022) · Immunology · doi:10.1111/imm.13588 · Cited by 96
“amino acids and fatty acids, may also play a role in exhaustion [60, 61].”
BackgroundChen, X., Sunkel, B. D., Wang, M., Kang, S., Wang, T., Gnanaprakasam, J. R., Liu, L., Cassel, T., Scott, D. A., Muñoz-Cabello, A. M., et al. (2022) · Science Immunology · doi:10.1126/sciimmunol.abm8161 · Cited by 94
“Beyond this, the availability of specific metabolites and the pathways that process them interconnect with signaling events and epigenetic regulators in the cell, orchestrating metabolic checkpoints that influence T cell activation, differentiation, and immune function (Birsoy et al., 2015; Chi, 2012; Gerriets and Rat…”
BackgroundMetabolism in the Tumor Microenvironment
Lau, A. N., & Heiden, M. G. V. (2019) · Annual Review of Cancer Biology · doi:10.1146/annurev-cancerbio-030419-033333 · Cited by 92
Wu, R., Chen, X., Kang, S., Wang, T., Gnanaprakasam, J. R., Yao, Y., Liu, L., Zheng, S. G., Fan, G., Burns, M. R., et al. (2020) · Science Advances · doi:10.1126/sciadv.abc4275 · Cited by 89
LKB 1 and AMPK : central regulators of lymphocyte metabolism and function
Blagih, J., Krawczyk, C. M., & Jones, R. G. (2012) · Immunological Reviews · doi:10.1111/j.1600-065x.2012.01157.x · Cited by 91
“In each phase of the immune response, T-cell metabolism must be matched to function to support T-cell survival, proliferation, and effector programs (4).”
BackgroundMacrophage proliferation, provenance, and plasticity in macroparasite infection
Rückerl, D., & Allen, J. E. (2014) · Immunological Reviews · doi:10.1111/imr.12221 · Cited by 87
Programmed necrosis and autophagy in immune function
Lu, J. V., & Walsh, C. M. (2012) · Immunological Reviews · doi:10.1111/j.1600-065x.2012.01147.x · Cited by 82
“As T cells switch from oxidative phosphorylation to an aerobic glycolytic metabolism following their activation through the TCR, they become less reliant on mitochondria for their source of energy (99).”
BackgroundChoileáin, S. N., Weyand, N. J., Neumann, C., Thomas, J., So, M., & Astier, A. (2011) · PLoS ONE · doi:10.1371/journal.pone.0016287 · Cited by 77
“These include regulation of cell death [2] and autophagy [3], upregulation of negative signaling molecules such as CTLA-4 [4] and PD-1 [5], metabolic amino-acid regulation [6,7], control by T regulatory (Treg) cells [8] and Treg induction by dendritic cells [9], among many others.”
BackgroundNaseem, S., Hussain, T., & Manzoor, S. (2018) · Cytokine & Growth Factor Reviews · doi:10.1016/j.cytogfr.2018.01.002 · Cited by 72
The relationship between CD4+ T cell glycolysis and their functions
Liu, S., Liao, S., Liang, L., Deng, J., & Zhou, Y. (2023) · Trends in Endocrinology and Metabolism · doi:10.1016/j.tem.2023.03.006 · Cited by 70
Perry, D. J., Yin, Y., Caza, T. N., Baker, H. V., Dozmorov, I. M., Perl, A., & Morel, L. M. (2012) · The Journal of Immunology · doi:10.4049/jimmunol.1200411 · Cited by 67
T-cell immunometabolism against cancer
Jiang, S., & Yan, W. (2016) · Cancer Letters · doi:10.1016/j.canlet.2016.09.003 · Cited by 66
Mitochondrial Retrograde Signalling and Metabolic Alterations in the Tumour Microenvironment
Yang, D., & Kim, J. (2019) · Cells · doi:10.3390/cells8030275 · Cited by 67
“They also differ across distinct cancers and are found even in non-transformed cells in the TME [21,22], indicating that metabolic flexibility can occur not only from genetic changes in genomic nDNA of cancer cells but also from modulation of metabolism by cells in the TME depending on the requirements of these cells…”
Peng, T., Zhu, J., Phasouk, K., Koelle, D. M., Wald, A., & Corey, L. (2012) · Journal of Virology · doi:10.1128/jvi.01237-12 · Cited by 63
“GLUT1, the primary glucose transporter in T lymphocytes, is transcriptionally expressed at low levels in resting T cells and both transcriptional induction and posttranslational trafficking are necessary for GLUT1-dependent glucose uptake during T-cell activation (6, 9), a process largely dependent on T-cell receptor…”
BackgroundNormal and cancer cell metabolism: lymphocytes and lymphoma
Altman, B. J., & Dang, C. V. (2012) · FEBS Journal · doi:10.1111/j.1742-4658.2012.08651.x · Cited by 66
Drivers of the Warburg Phenotype
Cairns, R. A. (2015) · The Cancer Journal · doi:10.1097/ppo.0000000000000106 · Cited by 63
“Workup to the present day, especially in T cells, has helped to define these metabolic changes in lymphocytes as they proliferate, differentiate, and adopt specific phenotypes.(17) It is now clear that a shift to a more glycolytic metabolism is required in order for T cells to proliferate in response to T-cell recepto…”
BackgroundExtracellular Lactate: A Novel Measure of T Cell Proliferation
Grist, J. T., Jarvis, L. B., Georgieva, Z. G., Thompson, S. A. J., Sandhu, H. K., Burling, K., Clarke, A., Jackson, S. E., Wills, M. R., Gallagher, F. A., et al. (2017) · The Journal of Immunology · doi:10.4049/jimmunol.1700886 · Cited by 59
“T cells have complex environment-dependent metabolic profiles, with different T cell subsets using different metabolic pathways to fuel their energy requirements (1, 2).”
BackgroundCalduch-Giner, J. À., Sitjà‐Bobadilla, A., & Pérez‐Sánchez, J. (2016) · Frontiers in Physiology · doi:10.3389/fphys.2016.00359 · Cited by 58
“Nutrient availability is also essential for the generation and maintenance of a protective effector immune system in humans and other model species (Fox et al., 2005; Michalek and Rathmell, 2010).”
BackgroundThe Effect of Malnutrition on Norovirus Infection
Hickman, D., Jones, M. K., Zhu, S., Roubidoux, E. K., Ostrov, D. A., Wang, X., Ukhanova, M., Sun, Y., Mai, V., Salemi, M., et al. (2014) · mBio · doi:10.1128/mbio.01032-13 · Cited by 56
Targeting T cell exhaustion: emerging strategies in non-small cell lung cancer
Liu, X., Xi, X., Xu, S., Chu, H., Hu, P., Li, D., Zhang, B., Liu, H., Jiang, T., & Lu, Z. (2024) · Frontiers in Immunology · doi:10.3389/fimmu.2024.1507501 · Cited by 52
The role of complement in CD4+ T cell homeostasis and effector functions
Kolev, M. V., Friec, G. L., & Kemper, C. (2013) · Seminars in Immunology · doi:10.1016/j.smim.2013.04.012 · Cited by 50
Optically-Gated Self-Calibrating Nanosensors: Monitoring pH and Metabolic Activity of Living Cells
Peretz‐Soroka, H., Pevzner, A., Davidi, G., Naddaka, V. I., Tirosh, R., Flaxer, E., & Patolsky, F. (2013) · Nano Letters · doi:10.1021/nl401169k · Cited by 50
Cusanovich, D. A., Billstrand, C., Zhou, X., Chavarria, C. I., Leon, S. D., Michelini, K., Pai, A. A., Ober, C., & Gilad, Y. (2012) · Human Molecular Genetics · doi:10.1093/hmg/dds021 · Cited by 49
“In addition, cellular proliferation, a central process of the lymphocyte response to antigen, is energetically taxing, and there is evidence suggesting that the metabolic pathways activated in T cells can influence not only sensitivity to apoptotic signals, but lineage decisions as well (58,59).”
BackgroundPromoting Thiol Expression Increases the Durability of Antitumor T-cell Functions
Kesarwani, P., Al-Khami, A. A., Scurti, G. M., Thyagarajan, K., Kaur, N., Husain, S., Fang, Q., Naga, O. S., Simms, P. E., Beeson, G. C., et al. (2014) · Cancer Research · doi:10.1158/0008-5472.can-14-1084 · Cited by 47
“While earlier reports have addressed the role of metabolism in T-cell activation and differentiation (12, 39, 40), its role in T-cell contraction and regulating antitumor response is beginning to be addressed (13, 41).”
MicroRNA-Mediated Restriction of HIV-1 in Resting CD4+ T Cells and Monocytes
Chiang, K., & Rice, A. P. (2012) · Viruses · doi:10.3390/v4091390 · Cited by 47
“Protein synthesis is also lower in resting cells [8], and overall a catabolic metabolism prevails, where ATP is generated from biosynthetic precursors like glucose via the TCA cycle and oxidative phosphorylation, supplying the minimum of energy needed to maintain housekeeping functions [23,24].”
BackgroundEarly Decision: Effector and Effector Memory T Cell Differentiation in Chronic Infection
Opata, M. M., & Stephens, R. (2014) · Current Immunology Reviews · doi:10.2174/1573395509666131126231209 · Cited by 46
Flora, G. D., Nayak, M. K., Ghatge, M., Kumskova, M., Patel, R. B., & Chauhan, A. K. (2023) · Blood Advances · doi:10.1182/bloodadvances.2023010100 · Cited by 43
Sim, S. W., Weinstein, D. A., Lee, Y., & Jun, H. S. (2019) · FEBS Letters · doi:10.1002/1873-3468.13666 · Cited by 45
Wu, S., Kuang, H., Ke, J., Pi, M., & Yang, D. (2021) · Frontiers in Oncology · doi:10.3389/fonc.2020.591342 · Cited by 43
“Regarded as quiescent population, naïve andmemory T cells mainly rely on OXPHOS and fatty acid b-oxidation (FAO) to produce ATP and show reduced rates of nutrient uptake and biosynthesis (34, 35).”
BackgroundTerminating the immune response
Marrack, P., Scott-Browne, J. P., & MacLeod, M. K. L. (2010) · Immunological Reviews · doi:10.1111/j.1600-065x.2010.00928.x · Cited by 43
“the glucose receptor Glut1 on the cell surface, thus helping the T cells take up glucose to use as fuel to drive proliferation (28).”
BackgroundInfluentialHan, X., Hu, S., Yang, Q., Sang, X., Tang, D., & Cao, G. (2021) · Phytomedicine · doi:10.1016/j.phymed.2021.153835 · Cited by 41
A critical role for Mnt in Myc-driven T-cell proliferation and oncogenesis
Link, J. M., Ota, S., Zhou, Z.-Q., Daniel, C. J., Sears, R. C., & Hurlin, P. J. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1206406109 · Cited by 38
Molecular Understanding of HIV-1 Latency
Abbas, W., & Herbein, G. (2012) · Advances in Virology · doi:10.1155/2012/574967 · Cited by 39
“These lymphocytes persist as memory cells with different pattern of gene expression for the long-term survival and rapid response to the relevant antigen in the future [144, 145].”
BackgroundMetabolic Disorders in Multiple Myeloma
Gavriatopoulou, M., Paschou, S. Α., Ntanasis‐Stathopoulos, I., & Dimopoulos, M. A. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms222111430 · Cited by 41
“Similarly, naïve and memory T cells mainly depend on OXPHOS and fatty acid β-oxidation (FAO) leading to ATP production [56,57].”
BackgroundQuantifying Biomass Changes of Single CD8+ T Cells during Antigen Specific Cytotoxicity
Zangle, T. A., Burnes, D., Mathis, C., Witte, O. N., & Teitell, M. A. (2013) · PLoS ONE · doi:10.1371/journal.pone.0068916 · Cited by 36
“Studies have shown that TCR agonists such as anti-CD3 antibodies or compounds that cause cross-linking of CD3 proteins result in a rapid and maximal induction of Glut1 expression [24,25].”
BackgroundWei, C.-W., Lee, C.-Y., Lee, D.-J., Chu, C.-F., Wang, J.-C., Wang, T.-C., Jane, W., Chang, Z.-F., Leu, C.-M., Dzhagalov, I. L., et al. (2018) · Cell Reports · doi:10.1016/j.celrep.2018.04.077 · Cited by 36
“Activated T cells transit their energy production from oxidative phosphorylation (OXPHOS) to glycolysis (Buck et al., 2015), and the ones that cannot fulfill this bioenergetic demand die by apoptosis (Michalek and Rathmell, 2010).”
BackgroundThe Ups and Downs of Metabolism during the Lifespan of a T Cell
Balyan, R., Gautam, N., & Gascoigne, N. R. J. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21217972 · Cited by 36
“After an igen learance, the cells that survive to become memor T cells return to a more quiescent oxid tive meta olism [31].”
BackgroundInfluentialKobliakov, V. A. (2019) · Biochemistry (Moscow) · doi:10.1134/s0006297919100018 · Cited by 34
Epigenetic Control of Cdkn2a.Arf Protects Tumor-Infiltrating Lymphocytes from Metabolic Exhaustion
Koss, B. S., Shields, B. D., Taylor, E. M., Storey, A. J., Byrum, S. D., Gies, A. J., Washam, C. L., Choudhury, S. R., Ahn, J. H., Uryu, H., et al. (2020) · Cancer Research · doi:10.1158/0008-5472.can-20-0524 · Cited by 33
“Loss of EZH2 function leads to metabolic exhaustion in CD8þ T cells T-cell activation leads to rapid and robust metabolic changes essential to support proliferation and function (35).”
BackgroundADP-dependent glucokinase regulates energy metabolism via ER-localized glucose sensing
Imle, R., Wang, B.-T., Stützenberger, N., Birkenhagen, J., Tandon, A., Carl, M., Himmelreich, N., Thiel, C., Gröne, H., Poschet, G., et al. (2019) · Scientific Reports · doi:10.1038/s41598-019-50566-6 · Cited by 32
Autophagy in T‐cell differentiation, survival and memory
Wang, L., Das, J. K., Kumar, A., Peng, H., Ren, Y., Xiong, X., Yang, J., & Song, J. J. (2020) · Immunology and Cell Biology · doi:10.1111/imcb.12422 · Cited by 31
“shifts from oxidative phosphorylation to glycolysis and increases its glucose consumption.(50) When the immune system has cleared the pathogen, most (approximate”
BackgroundBarberis, M., & López, A. R. (2024) · Clinical and Translational Medicine · doi:10.1002/ctm2.1626 · Cited by 29
“9 An important aspect of T-cell metabolism is the dynamic of protein synthesis and degradation, which contribute to the demand for energy and amino acids during T-cell activation, proliferation and differentiation.”
BackgroundJiang, Y., Tu, X., Zhang, X., Liao, H., Han, S., Jiang, W., Zheng, Y., Zhao, P., Tong, Z., Fu, Q., et al. (2020) · Supportive Care in Cancer · doi:10.1007/s00520-020-05478-x · Cited by 27
“In contrast, regulatory T cells (Treg) and memory T cells (TMEM) have reduced glucose metabolism, mainly using lipid oxidation to promote inhibition and memory function [26, 27].”
BackgroundThe role of tumor metabolism in modulating T-Cell activity and in optimizing immunotherapy
Ganjoo, S., Gupta, P., Corbali, H. I., Nanez, S., Riad, T. S., Duong, L. K., Barsoumian, H. B., Masrorpour, F., Jiang, H., Welsh, J. W., et al. (2023) · Frontiers in Immunology · doi:10.3389/fimmu.2023.1172931 · Cited by 32
“Frontiers in Immunology 05 acid transporters after activation (99).”
BackgroundMetabolic Defects of Peripheral T Cells in COVID-19 Patients
Liu, X., Zhao, J., Wang, H., Wang, W., Su, X., Liao, X., Zhang, S., Sun, J., & Zhang, Z. (2021) · The Journal of Immunology · doi:10.4049/jimmunol.2100068 · Cited by 27
Kabiraj, P., Grund, E. M., Clarkson, B. D. S., Johnson, R. K., LaFrance‐Corey, R. G., Lucchinetti, C. F., & Howe, C. L. (2022) · Scientific Reports · doi:10.1038/s41598-022-07024-7 · Cited by 26
Immune Modulation in Lung Cancer: Current Concepts and Future Strategies
Gaissmaier, L., & Christopoulos, P. (2020) · Respiration · doi:10.1159/000510385 · Cited by 24
Cereblon harnesses Myc-dependent bioenergetics and activity of CD8+ T lymphocytes
Hesterberg, R. S., Beatty, M. S., Han, Y., Fernandez, M. R., Akuffo, A. A., Goodheart, W. E., Yang, C., Chang, S., Colin, C., Alontaga, A. Y., et al. (2020) · Blood · doi:10.1182/blood.2019003257 · Cited by 22
Ilievski, V., Kinchen, J. M., Prabhu, R., Rim, F., Leoni, L., Unterman, T. G., & Watanabe, K. (2016) · Journal of Oral Biology · doi:10.13188/2377-987x.1000020 · Cited by 22
“Activated immune cells are highly glycolytic [25,26] and infiltration of immune cells into the heart could contribute to changes in observed energy metabolism.”
Seeing the Warburg effect in the developing retina
Fiske, B. P., & Heiden, M. G. V. (2012) · Nature Cell Biology · doi:10.1038/ncb2554 · Cited by 21
Coefficient of energy balance, a new parameter for basic investigation of the cerebrospinal fluid
Kelbich, P., Hejčl, A., Krulichová, I. S., Procházka, J., Hanuljaková, E., Peruthová, J., Koudelková, M., Sameš, M., & Krejsek, J. (2014) · Clinical Chemistry and Laboratory Medicine (CCLM) · doi:10.1515/cclm-2013-0953 · Cited by 20
Wang, Y., Torres‐García, D., Mostert, T. P., Reinalda, L., & van Kasteren, S. I. (2024) · Angewandte Chemie International Edition · doi:10.1002/anie.202401733 · Cited by 19
Metadata
- 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
- 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
- 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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