AMPK α1: A glucose sensor that controls CD 8 T ‐cell memory
Open accessAbstract
The adenosine monophosphate-activated protein kinase (AMPK) is activated by antigen receptor signals and energy stress in T cells. In many cell types, AMPK can maintain energy homeostasis and can enforce quiescence to limit energy demands. We consequently evaluated the importance of AMPK for controlling the transition of metabolically active effector CD8 T lymphocytes to the metabolically quiescent catabolic memory T cells during the contraction phase of the immune response. We show that AMPKα1 activates rapidly in response to the metabolic stress caused by glucose deprivation of CD8 cytotoxic T lymphocytes (CTLs). Moreover, AMPKα1 restrains mammalian target of rapamycin complex 1 activity under conditions of glucose stress. AMPKα1 activity is dispensable for proliferation and differentiation of CTLs. However, AMPKα1 is required for in vivo survival of CTLs following withdrawal of immune stimulation. AMPKα1(null) T cells also show a striking defect in their ability to generate memory CD8 T-cell responses during Listeria monocytogenes infection. These results show that AMPKα1 monitors energy stress in CTLs and controls CD8 T-cell memory.
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Reducing or increasing AMPK, a positive regulator of fatty acid oxidation, respectively decreases or increases memory T cell formation.
“The importance of fatty acid oxidation for Tm cells is bolstered by the observations that diminishing or enhancing AMPK, a positive regulator of fatty acid oxidation, decreases or increases formation of memory T cells (MacIver et al., 2011; Pearce et al., 2009; Rolf et al., 2013; Tamás et al., 2010).”
From Mitochondria in the Regulation of Innate and Adaptive Immunity (2015) · cites this paper as Rolf et al., 2013
AMPK-deficient T cells are defective in their ability to generate CD8+ memory T cells during infection.
“Furthermore, it was recently shown that AMPK-deficient T cells are defective in their ability to generate CD8+ memory T cells during infection (92).”
From Fueling Immunity: Insights into Metabolism and Lymphocyte Function (2013) · cites this paper as [92]
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Cites
AMPK: a nutrient and energy sensor that maintains energy homeostasis
Hardie, D. G., Ross, F. A., & Hawley, S. A. (2012) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3311 · Cited by 4,602 · see citing works
TSC2 Mediates Cellular Energy Response to Control Cell Growth and Survival
Inoki, K., Zhu, T., & Guan, K.-L. (2003) · Cell · doi:10.1016/s0092-8674(03)00929-2 · Cited by 3,914 · see citing works
AMPK Phosphorylation of Raptor Mediates a Metabolic Checkpoint
Gwinn, D. M., Shackelford, D. B., Egan, D. F., Mihaylova, M. M., Mery, A., Vasquez, D. S., Turk, B. E., & Shaw, R. J. (2008) · Molecular Cell · doi:10.1016/j.molcel.2008.03.003 · Cited by 3,849 · see citing works
T cell receptor antagonist peptides induce positive selection.
Hogquist, K., Jameson, S., Heath, W., Howard, J. L., Bevan, M., & Carbone, F. (1994) · Cell · doi:10.1016/0092-8674(94)90169-4 · Cited by 3,252 · see citing works
The transcription factor Myc controls metabolic reprogramming upon T lymphocyte activation
Wang, R., Dillon, C. P., Shi, L. Z., Milasta, S., Carter, R., Finkelstein, D., McCormick, L. L., Fitzgerald, P., Chi, H., Munger, J., et al. (2011) · Immunity · doi:10.1016/j.immuni.2011.09.021 · Cited by 2,140 · see citing works
Michalek, R. D., Gerriets, V. A., Jacobs, S. R., Macintyre, A. N., MacIver, N. J., Mason, E. F., Sullivan, S. A., Nichols, A. G., & Rathmell, J. C. (2011) · The Journal of Immunology · doi:10.4049/jimmunol.1003613 · Cited by 2,091 · see citing works
mTOR regulates memory CD8 T-cell differentiation
Araki, K., Turner, A. P., Shaffer, V. O., Gangappa, S., Keller, S. A., Bachmann, M. F., Larsen, C. P., & Ahmed, R. (2009) · Nature · doi:10.1038/nature08155 · Cited by 1,575 · see citing works
Enhancing CD8 T-cell memory by modulating fatty acid metabolism
Pearce, E. L., Walsh, M. C., Cejas, P. J., Harms, G. M., Shen, H., Wang, L.-S., Jones, R. G., & Choi, Y. (2009) · Nature · doi:10.1038/nature08097 · Cited by 1,559 · see citing works
Mitochondrial respiratory capacity is a critical regulator of CD8+ T cell memory development
van der Windt, G. J. W., Everts, B., Chang, C.-H., Curtis, J. D., Freitas, T. C., Amiel, E., Pearce, E. J., & Pearce, E. L. (2012) · Immunity · doi:10.1016/j.immuni.2011.12.007 · Cited by 1,540 · see citing works
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 · see citing works
Foretz, M., Hébrard, S., Leclerc, J., Zarrinpashneh, E., Soty, M., Mithieux, G., Sakamoto, K., Andreelli, F., & Viollet, B. (2010) · Journal of Clinical Investigation · doi:10.1172/jci40671 · Cited by 1,181 · see citing works
Self-citationMetformin, independent of AMPK, inhibits mTORC1 in a rag GTPase-dependent manner
Kalender, A., Selvaraj, A., Kim, S. Y., Gulati, P., Brûlé, S., Viollet, B., Kemp, B. E., Bardeesy, N., Dennis, P., Schlager, J. J., et al. (2010) · Cell Metabolism · doi:10.1016/j.cmet.2010.03.014 · Cited by 889 · see citing works
Self-citationJacobs, S. R., Herman, C. E., MacIver, N. J., Wofford, J. A., Wieman, H. L., Hammen, J. J., & Rathmell, J. C. (2008) · The Journal of Immunology · doi:10.4049/jimmunol.180.7.4476 · Cited by 853 · see citing works
Rao, R. R., Li, Q., Odunsi, K., & Shrikant, P. A. (2010) · Immunity · doi:10.1016/j.immuni.2009.10.010 · Cited by 656 · see citing works
Functional and genomic profiling of effector CD8 T cell subsets with distinct memory fates
Sarkar, S., Kalia, V., Haining, W. N., Konieczny, B. T., Subramaniam, S., & Ahmed, R. (2008) · The Journal of Experimental Medicine · doi:10.1084/jem.20071641 · Cited by 633 · see citing works
Transient expression of interleukin 2 receptors. Consequences for T cell growth.
Cantrell, D. A., & Smith, K. A. (1983) · The Journal of Experimental Medicine · doi:10.1084/jem.158.6.1895 · Cited by 607 · see citing works
Self-citationRathmell, 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 · see citing works
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 · see citing works
Aerobic glycolysis during lymphocyte proliferation
Wang, T., Marquardt, C. A., & Foker, J. E. (1976) · Nature · doi:10.1038/261702a0 · Cited by 333 · see citing works
Tamás, P., Hawley, S. A., Clarke, R. G., Mustard, K. J., Green, K., Hardie, D. G., & Cantrell, D. A. (2006) · The Journal of Experimental Medicine · doi:10.1084/jem.20052469 · Cited by 328 · see citing works
Self-citationMacintyre, A. N., Finlay, D. K., Preston, G., Sinclair, L. V., Waugh, C. M., Tamas, P., Feijóo, C. G., Okkenhaug, K., & Cantrell, D. A. (2011) · Immunity · doi:10.1016/j.immuni.2011.01.012 · Cited by 274 · see citing works
Self-citationThe 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 · see citing works
Generation of CD8 T Cell Memory Is Regulated by IL-12
Pearce, E. L., & Shen, H. (2007) · The Journal of Immunology · doi:10.4049/jimmunol.179.4.2074 · Cited by 228 · see citing works
Pathogen induced inflammatory environment controls effector and memory CD8+ T cell differentiation
Obar, J., Jellison, E., Sheridan, B., Blair, D., Pham, Q.-M., Zickovich, J. M., & Lefrançois, L. (2011) · Journal of Immunology · doi:10.4049/jimmunol.1102335 · Cited by 193 · see citing works
Differential regulation of T-cell growth by IL-2 and IL-15
Cornish, G. H., Sinclair, L. V., & Cantrell, D. A. (2006) · Blood · doi:10.1182/blood-2005-12-4827 · Cited by 175 · see citing works
Self-citationSignaling Takes a Breath – New Quantitative Perspectives on Bioenergetics and Signal Transduction
Krauss, S., Brand, M. D., & Buttgereit, F. (2001) · Immunity · doi:10.1016/s1074-7613(01)00205-9 · Cited by 147 · see citing works
Mayer, A., Denanglaire, S., Viollet, B., Léo, O., & Andris, F. (2008) · European Journal of Immunology · doi:10.1002/eji.200738045 · Cited by 98 · see citing works
Self-citationSurviving the crash: Transitioning from effector to memory CD8+ T cell
D’Cruz, L. M., Rubinstein, M. P., & Goldrath, A. W. (2009) · Seminars in Immunology · doi:10.1016/j.smim.2009.02.002 · Cited by 88 · see citing works
Waugh, C. M., Sinclair, L. V., Finlay, D. K., Bayascas, J. R., & Cantrell, D. A. (2009) · Molecular and Cellular Biology · doi:10.1128/mcb.00585-09 · Cited by 77 · see citing works
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L-Arginine Modulates T Cell Metabolism and Enhances Survival and Anti-tumor Activity
Geiger, R., Rieckmann, J. C., Wolf, T., Basso, C., Feng, Y., Fuhrer, T., Kogadeeva, M., Picotti, P., Meissner, F., Mann, M., et al. (2016) · Cell · doi:10.1016/j.cell.2016.09.031 · Cited by 1,775 · see citing works
Fueling Immunity: Insights into Metabolism and Lymphocyte Function
Pearce, E. L., Poffenberger, M. C., Chang, C.-H., & Jones, R. G. (2013) · Science · doi:10.1126/science.1242454 · Cited by 1,363 · see citing works
Metabolism of Inflammation Limited by AMPK and Pseudo-Starvation
O'Neill, L. A. J., & Hardie, D. G. (2013) · Nature · doi:10.1038/nature11862 · Cited by 1,133 · see citing works
Mitochondria in the Regulation of Innate and Adaptive Immunity
Weinberg, S. E., Sena, L. A., & Chandel, N. S. (2015) · Immunity · doi:10.1016/j.immuni.2015.02.002 · Cited by 960 · see citing works
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 · see citing works
Gowans, G. J., Hawley, S. A., Ross, F. A., & Hardie, D. G. (2013) · Cell Metabolism · doi:10.1016/j.cmet.2013.08.019 · Cited by 531 · see citing works
Autophagy is a critical regulator of memory CD8+ T cell formation
Puleston, D. J., Zhang, H., Powell, T. J., Lipina, E., Sims, S., Panse, I., Watson, A. S., Cerundolo, V., Townsend, A. R., Klenerman, P., et al. (2014) · eLife · doi:10.7554/elife.03706 · Cited by 360 · see citing works
Lanna, A., Henson, S. M., Escors, D., & Akbar, A. N. (2014) · Nature Immunology · doi:10.1038/ni.2981 · Cited by 328 · see citing works
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Fang, F., Yu, M., Cavanagh, M. M., Hutter Saunders, J., Qi, Q., Ye, Z., Le Saux, S., Sultan, W., Turgano, E., Dekker, C. L., et al. (2016) · Cell Reports · doi:10.1016/j.celrep.2016.01.002 · Cited by 138 · see citing works
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- Authors
- Rolf, J., Zarrouk, M., Finlay, D. K., Foretz, M., Viollet, B., & Cantrell, D. A.
- Affiliations
- University of Dundee (GB)
- Centre National de la Recherche Scientifique (FR)
- Inserm, U1016, Institut Cochin, Cnrs, UMR8104 Université Paris Descartes Sorbonne Paris Cité France
- Corresponding author
- Cantrell, Doreen A.
- Venue
- European Journal of Immunology
- Publisher
- Wiley
- Published
- 2013-02-13
- Volume
- 43
- Issue
- 4
- Pages
- 889-896
- ISSN
- 0014-2980 (ISSN-L)
- 1521-4141
- PMC
- PMC3734624
- OpenAlex
- W1882193637
- Cited by
- 245
- References
- 29
- Citations by year
- 2026: 13 · 2025: 18 · 2024: 16 · 2023: 10 · 2022: 13 · 2021: 27 · 2020: 26 · 2019: 20 · 2018: 17 · 2017: 23 · 2016: 20 · 2015: 18 · 2014: 12 · 2013: 12
- FWCI
- 11.42
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- European Journal of Immunology (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Discovery Research Portal (University of Dundee) (publishedVersion)
- Arrow@dit (Dublin Institute of Technology) (submittedVersion)
- Funders
- Wellcome Trust (097418/Z/11/Z, 065975, 097418)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Biochemical and Molecular Research
- Keywords
- AMPKα1, CD8+ T cell memory, cytotoxic T lymphocytes, glucose deprivation, energy stress, metabolic quiescence, mTORC1, T cell contraction, Listeria monocytogenes infection, T cell survival
- MeSH terms
- Animals, Cells, Cultured, Glucose, Immunologic Memory, T-Lymphocytes, Cytotoxic, CD8-Positive T-Lymphocytes, Mice, AMP-Activated Protein Kinases
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