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- W4313374503 abstract "Abstract The ability of T cells to sense and respond to environmental cues by altering their functional capabilities is critical for a safe and optimally protective immune response. One of the important properties that contributes to this goal is the activation setpoint of the T cell. Here we report a new pathway through which CD8+ T cells can self-tune their activation threshold. We find that in the presence of a strong TCR engagement event, there is a shift in the metabolic programming of the cell where both glycolysis and oxidative phosphorylation are significantly increased. This diverges from the switch to a predominantly glycolytic profile that would be predicted following naïve T cell activation. This altered metabolic program results in the production of autocrine IL-4. Both metabolic pathways are required for this cytokine to be made. IL-4 signaling in the activated CD8+ T cell results in modulation of the sensitivity of the cell, establishing a higher activation setpoint that is maintained over time. Together these data demonstrate a novel mechanism for the regulation of IL-4 production in CD8+ T cells. Further, they reveal a new pathway for the self-tuning of peptide sensitivity. Finally, these studies uncover an unexpected role for oxidative phosphorylation in regulating differentiation in CD8+ T cells." @default.
- W4313374503 created "2023-01-06" @default.
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- W4313374503 date "2020-05-01" @default.
- W4313374503 modified "2023-09-25" @default.
- W4313374503 title "TCR dependent metabolic programming regulates autocrine IL-4 production resulting in self-tuning of the CD8+ T cell activation setpoint" @default.
- W4313374503 doi "https://doi.org/10.4049/jimmunol.204.supp.77.5" @default.
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