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Characterization of the metabolic phenotype of rapamycin-treated CD8+ T cells with augmented ability to generate long-lasting memory cells
Journal article   Open access

Characterization of the metabolic phenotype of rapamycin-treated CD8+ T cells with augmented ability to generate long-lasting memory cells

Shan He, Koji Kato, Jiu Jiang, Daniel R Wahl, Shin Mineishi, Erin M Fisher, Donna M Murasko, Gary D Glick and Yi Zhang
PloS one, v 6(5), pp e20107-e20107
2011
DOI: https://doi.org/10.1371/journal.pone.0020107
PMID: 21611151
Featured in Collection :   UN Sustainable Development Goals @ Drexel
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https://doi.org/10.1371/journal.pone.0020107View
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Abstract

CD8-Positive T-Lymphocytes - cytology Cell Survival - drug effects Reactive Oxygen Species - metabolism Glucose - pharmacology Immunologic Memory - drug effects Membrane Potential, Mitochondrial - drug effects Glycolysis - drug effects Sirolimus - pharmacology Oxidative Phosphorylation - drug effects Glucose - deficiency Phenotype Animals Oligomycins - pharmacology Intercellular Signaling Peptides and Proteins - pharmacology CD8-Positive T-Lymphocytes - drug effects Interleukin-2 - deficiency CD8-Positive T-Lymphocytes - metabolism Interleukin-2 - pharmacology Mice Intercellular Signaling Peptides and Proteins - deficiency
Cellular metabolism plays a critical role in regulating T cell responses and the development of memory T cells with long-term protections. However, the metabolic phenotype of antigen-activated T cells that are responsible for the generation of long-lived memory cells has not been characterized. Using lymphocytic choriomeningitis virus (LCMV) peptide gp33-specific CD8(+) T cells derived from T cell receptor transgenic mice, we characterized the metabolic phenotype of proliferating T cells that were activated and expanded in vitro in the presence or absence of rapamycin, and determined the capability of these rapamycin-treated T cells to generate long-lived memory cells in vivo. Antigen-activated CD8(+) T cells treated with rapamycin gave rise to 5-fold more long-lived memory T cells in vivo than untreated control T cells. In contrast to that control T cells only increased glycolysis, rapamycin-treated T cells upregulated both glycolysis and oxidative phosphorylation (OXPHOS). These rapamycin-treated T cells had greater ability than control T cells to survive withdrawal of either glucose or growth factors. Inhibition of OXPHOS by oligomycin significantly reduced the ability of rapamycin-treated T cells to survive growth factor withdrawal. This effect of OXPHOS inhibition was accompanied with mitochondrial hyperpolarization and elevation of reactive oxygen species that are known to be toxic to cells. Our findings indicate that these rapamycin-treated T cells may represent a unique cell model for identifying nutrients and signals critical to regulating metabolism in both effector and memory T cells, and for the development of new methods to improve the efficacy of adoptive T cell cancer therapy.

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Collaboration types
Domestic collaboration
Web of Science research areas
Immunology
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