biostudies-literatureUnknown11Crofts KFNational Institutes of HealthThe 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 set-point of the T cell. Here we report a new pathway through which TCR transgenic OT-I 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. Our data suggest this altered metabolic program results in the prFrontiers in immunology540https://www.ebi.ac.uk/biostudies/studies/S-EPMC7145404biostudies-literatureTCR Dependent Metabolic Programming Regulates Autocrine IL-4 Production Resulting in Self-Tuning of the CD8⁺ T Cell Activation Setpoint.PMC7145404Holbrook BCOrnelles DAAlexander-Miller MASoto-Pantoja DRCrofts KFfalseTCR Dependent Metabolic Programming Regulates Autocrine IL-4 Production Resulting in Self-Tuning of the CD8⁺ T Cell Activation Setpoint.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 set-point of the T cell. Here we report a new pathway through which TCR transgenic OT-I 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. Our data suggest this altered metabolic program results in the pr2020-01-01T00:00:00Z20202025-04-04T07:20:42.024Z2020-05-22T17:27:23ZS-EPMC71454043230034410.3389/fimmu.2020.00540