Fever supports CD8+effector T cell responses by mitochondrial translation

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 degrees 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 degrees 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 degrees 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.

Automated summary

Fever can enhance metabolic activity and effector functions of activated CD8* T cells, with limited effects on proliferation or activation marker expression. Exposure to 39 degrees Celsius increases mass and metabolism in T cells, with mitochondrial translation playing a crucial role in the enhanced metabolic activity and function observed.