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

Area of Science:

• Immunology
• Cellular Metabolism
• Thermobiology

Background:

• Fever is known to aid survival during infections.
• The impact of fever on T cell metabolism remains poorly understood.
• Metabolic processes are sensitive to environmental temperature changes.

Purpose of the Study:

• To investigate the effects of febrile temperatures on T cell metabolism and function.
• To elucidate the molecular mechanisms underlying temperature-induced changes in T cells.
• To explore the therapeutic potential of fever-conditioned T cells in cancer treatment.

Main Methods:

• Activation of CD8+ T cells and exposure to febrile temperatures (39 °C).
• Transcriptional profiling to analyze gene expression changes.
• In vitro and in vivo experiments using mouse models.
• Assessment of T cell proliferation, activation, metabolism, and effector functions.

Main Results:

• Febrile temperatures augmented metabolic activity and effector functions in activated CD8+ T cells.
• Transcriptional profiling indicated upregulation of mitochondrial pathways.
• Increased mitochondrial mass and metabolism were observed in T cells at 39 °C.
• Mitochondrial translation was identified as crucial for enhanced T cell function at febrile temperatures.
• Pre-infusion exposure of lymphocytes to 39 °C improved therapeutic efficacy in a myeloid leukemia mouse model.

Conclusions:

• Febrile temperatures enhance CD8+ T cell metabolic activity and effector functions, primarily through mitochondrial pathways.
• Mitochondrial translation plays a key role in fever-induced T cell augmentation.
• Exposing T cells to febrile temperatures ex vivo may offer a novel strategy for enhancing cancer immunotherapy.