Memory CD8+ T Cells Use Cell-Intrinsic Lipolysis to Support the Metabolic Programming Necessary for Development
Open accessAbstract
Generation of CD8(+) memory T cells requires metabolic reprogramming that is characterized by enhanced mitochondrial fatty-acid oxidation (FAO). However, where the fatty acids (FA) that fuel this process come from remains unclear. While CD8(+) memory T cells engage FAO to a greater extent, we found that they acquired substantially fewer long-chain FA from their external environment than CD8(+) effector T (Teff) cells. Rather than using extracellular FA directly, memory T cells used extracellular glucose to support FAO and oxidative phosphorylation (OXPHOS), suggesting that lipids must be synthesized to generate the substrates needed for FAO. We have demonstrated that memory T cells rely on cell intrinsic expression of the lysosomal hydrolase LAL (lysosomal acid lipase) to mobilize FA for FAO and memory T cell development. Our observations link LAL to metabolic reprogramming in lymphocytes and show that cell intrinsic lipolysis is deterministic for memory T cell fate.
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FAO is fundamental for the survival and function of memory CD8+ T cells, unlike effector cells that rely on glycolysis and glutaminolysis for energy.
“FAO is fundamental for the survival and function of memory CD8+ T cells, unlike effector cells that rely on glycolysis and glutaminolysis for energy.60,61”
From The multifaceted contributions of mitochondria to cellular metabolism (2018) · cites this paper as [61]
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- Authors
- O’Sullivan, D., van der Windt, G. J. W., Huang, S. C.-C., Curtis, J. D., Chang, C.-H., Buck, M. D., Qiu, J., Smith, A. M., Lam, W. Y., DiPlato, L. M., Hsu, F.-F., Birnbaum, M. J., Pearce, E. J., & Pearce, E. L.
- Affiliations
- Washington University in St. Louis (US)
- University of Pennsylvania (US)
- Corresponding author
- Pearce, Erika L.
- ORCID
- Venue
- Immunity
- Publisher
- Elsevier BV
- Published
- 2014-07
- Volume
- 41
- Issue
- 1
- Pages
- 75-88
- ISSN
- 1074-7613 (ISSN-L)
- PMC
- PMC4120664
- OpenAlex
- W2131199230
- Cited by
- 790
- References
- 66
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- FWCI
- 26.63
- Type
- journal article
- Language
- en
- Update notices
- erratum (2018-08-21)
- Open access
- bronze
- doi.org
- Licence
- Locations
- Immunity (publishedVersion)
- PubMed (publishedVersion)
- Pure Amsterdam UMC (publishedVersion)
- PubMed Central (acceptedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Pure Amsterdam UMC (submittedVersion)
- MPG.PuRe (Max Planck Society) (submittedVersion, other-oa)
- Funders
- National Institutes of Health
- National Cancer Institute (CA158823, CA164062, R21CA158823, R01CA164062, R01CA181125)
- National Institute of General Medical Sciences (P41GM103422)
- National Institute of Allergy and Infectious Diseases (R01AI091965, AI 091965)
- National Institute of Diabetes and Digestive and Kidney Diseases (P30DK056341, P30DK020579)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Lipid metabolism and biosynthesis
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Lipids, and Metabolism
- Keywords
- memory CD8+ T cells, fatty acid oxidation, lysosomal acid lipase, metabolic reprogramming, long-chain fatty acids, oxidative phosphorylation, lipogenesis, effector T cells, T cell metabolism
- MeSH terms
- Animals, Cell Survival, Cells, Cultured, Sterol Esterase, Fatty Acids, Glucose, Immunologic Memory, Interleukin-2, Lipolysis, Lymphocyte Activation, Mice, Inbred C57BL, Mice, Transgenic, Mitochondria, Oxidation-Reduction, Oxidative Phosphorylation, Oxygen, Protein Kinases, 4-Butyrolactone, CD8-Positive T-Lymphocytes, Adoptive Transfer, Interleukin-15, RNA Interference, RNA, Small Interfering, Cell Proliferation, Mice, Fatty Acid Synthases
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