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CD8 memory T cells have a bioenergetic advantage that underlies their rapid recall ability
Open accessAbstract
A characteristic of memory T (T M ) cells is their ability to mount faster and stronger responses to reinfection than naïve T (T N ) cells do in response to an initial infection. However, the mechanisms that allow this rapid recall are not completely understood. We found that CD8 T M cells have more mitochondrial mass than CD8 T N cells and, that upon activation, the resulting secondary effector T (T E ) cells proliferate more quickly, produce more cytokines, and maintain greater ATP levels than primary effector T cells. We also found that after activation, T M cells increase oxidative phosphorylation and aerobic glycolysis and sustain this increase to a greater extent than T N cells, suggesting that greater mitochondrial mass in T M cells not only promotes oxidative capacity, but also glycolytic capacity. We show that mitochondrial ATP is essential for the rapid induction of glycolysis in response to activation and the initiation of proliferation of both T N and T M cells. We also found that fatty acid oxidation is needed for T M cells to rapidly respond upon restimulation. Finally, we show that dissociation of the glycolysis enzyme hexokinase from mitochondria impairs proliferation and blocks the rapid induction of glycolysis upon T-cell receptor stimulation in T M cells. Our results demonstrate that greater mitochondrial mass endows T M cells with a bioenergetic advantage that underlies their ability to rapidly recall in response to reinfection.
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“We have recently shown that increased mitochondrial mass and SRC of TM cells allows for rapid mitochondrial ATP production upon TCR engagement, conferring a bioenergetic advantage to TM cells upon secondary exposure to antigen (16).”
From Fueling Immunity: Insights into Metabolism and Lymphocyte Function (2013) · cites this paper as [16]
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Metadata
- Authors
- van der Windt, G. J. W., O’Sullivan, D., Everts, B., Huang, S. C.-C., Buck, M. D., Curtis, J. D., Chang, C.-H., Smith, A. M., Ai, T., Faubert, B., Jones, R. G., Pearce, E. J., & Pearce, E. L.
- Affiliations
- Department of Pathology and Immunology, Washington University School of Medicine in St. Louis, St. Louis, MO 63110; and
- Washington University in St. Louis (US)
- McGill University (CA)
- ORCID
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2013-08-12
- Volume
- 110
- Issue
- 35
- Pages
- 14336-14341
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC3761631
- OpenAlex
- W2061318708
- Cited by
- 523
- References
- 39
- Citations by year
- 2026: 27 · 2025: 29 · 2024: 27 · 2023: 40 · 2022: 50 · 2021: 54 · 2020: 55 · 2019: 56 · 2018: 44 · 2017: 46 · 2016: 44 · 2015: 30 · 2014: 19 · 2013: 2
- FWCI
- 17.50
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Pure Amsterdam UMC (submittedVersion)
- MPG.PuRe (Max Planck Society) (submittedVersion, other-oa)
- Funders
- National Cancer Institute (R01CA164062)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
- Keywords
- memory CD8+ T cells, mitochondrial mass, recall response, oxidative phosphorylation, aerobic glycolysis, fatty acid oxidation, hexokinase, mitochondrial ATP, T cell proliferation, T cell receptor stimulation, cytokine production
- MeSH terms
- Animals, Energy Metabolism, Immunologic Memory, Lymphocyte Activation, CD8-Positive T-Lymphocytes, Mice, Mitochondrial Size
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