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Fever supports CD8⁺ effector T cell responses by promoting mitochondrial translation.

ABSTRACT: Fever can provide a survival advantage during infection. Metabolic processes are sensitive to environmental conditions, but the effect of fever on T cell metabolism is not well characterized. We show that in activated CD8⁺ T cells, exposure to febrile temperature (39 °C) augmented metabolic activity and T cell effector functions, despite having a limited effect on proliferation or activation marker expression. Transcriptional profiling revealed an up-regulation of mitochondrial pathways, which was consistent with increased mass and metabolism observed in T cells exposed to 39 °C. Through in vitro and in vivo models, we determined that mitochondrial translation is integral to the enhanced metabolic activity and function of CD8⁺ T cells exposed to febrile temperature. Transiently exposing donor lymphocytes to 39 °C prior to infusion in a myeloid leukemia mouse model conferred enhanced therapeutic efficacy, raising the possibility that exposure of T cells to febrile temperatures could have clinical potential.

SUBMITTER: O'Sullivan D

PROVIDER: S-EPMC8237659 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Fever supports CD8+ effector T cell responses by promoting mitochondrial translation

Project description:Fever can provide a survival advantage during infection. Metabolic processes are sensitive to environmental conditions, but the effect of fever on T cell metabolism is not well characterized. We show that in activated CD8+ T cells, exposure to febrile temperature (39°C) augmented metabolic activity and T cell effector functions, despite having a limited effect on proliferation or activation marker expression. Transcriptional profiling revealed an upregulation of mitochondrial pathways, which was consistent with increased mitochondrial metabolism and mass observed in T cells exposed to 39°C. Through in vitro and in vivo models we determined that mitochondrial translation is integral to the enhanced metabolic activity and function of CD8+ T cells exposed to febrile temperature. Transiently exposing donor lymphocytes to 39°C prior to infusion in a myeloid leukemia (ML) mouse model conferred enhanced therapeutic efficacy, raising the possibility that exposure of T cells to febrile temperatures could have clinical potential.

2021-07-02 | GSE171245 | GEO

Fever supports CD8+ effector T cell responses by promoting mitochondrial translation

Project description:Fever supports CD8+ effector T cell responses by promoting mitochondrial translation

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Intratumoral delivery of mTORC2-deficient dendritic cells inhibits B16 melanoma growth by promoting CD8(+) effector T cell responses.

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STAT5 is critical to maintain effector CD8+ T cell responses.

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Toll-Like Receptor 7 Activation Enhances CD8+ T Cell Effector Functions by Promoting Cellular Glycolysis.

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