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Immunity. 2014 Jul 17;41(1):75-88. doi: 10.1016/j.immuni.2014.06.005. Epub 2014 Jul 4.

Memory CD8(+) T cells use cell-intrinsic lipolysis to support the metabolic programming necessary for development.

Author information

1
Department of Pathology & Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.
2
The Institute for Diabetes, Obesity, and Metabolism, University of Pennsylvania, Philadelphia, PA 19104, USA.
3
Mass Spectrometry Resource, Division of Endocrinology, Diabetes, Metabolism, and Lipid Research, Department of Internal Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA.
4
Department of Pathology & Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA. Electronic address: erikapearce@path.wustl.edu.

Abstract

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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PMID:
25001241
PMCID:
PMC4120664
DOI:
10.1016/j.immuni.2014.06.005
[Indexed for MEDLINE]
Free PMC Article

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