Cardiorespiratory Fitness Predicts Aspects Of CD8 T Cell Function And Metabolism

Cardiorespiratory fitness (CRF) indicates the health of several body systems. How CRF relates to specific immune cells such as cytotoxic CD8+ T cells (Tc) is less understood. Tc use cytokines, such as interferon (IFN)-γ, to respond to viral infections and tumors. This requires increased energy production. Higher CRF is associated with greater metabolism across many cell types. Thus, enhanced metabolism associated with higher CRF may provide energy to support Tc cytokine production. PURPOSE: Examine the relationship between CRF and Tc function and metabolism. METHODS: 28 adults (11 women, 28.9 ± 6.2 years) donated blood after an overnight fast. CRF, indicated by VO2max, was assessed by graded cardiopulmonary exercise testing to exhaustion on a cycle ergometer. Tc function, represented by IFN-γ expression, was assessed by flow cytometry pre and post stimulation of peripheral mononuclear cells with PMA and ionomycin. Tc metabolism was assessed using single cell energetic metabolism by profiling translation inhibition (SCENITH). Tc puromycin incorporation (representing ATP synthesis) was measured by flow cytometry pre and post inhibition of oxidative and/or glycolytic metabolism to indicate mitochondrial dependence, glycolytic dependence, glycolytic capacity, and fatty acid/amino acid oxidation. Linear regression tested whether CRF predicted Tc function or Tc metabolism. RESULTS: VO2max ranged from 23.90-57.61 mLO2/kg/min. The regression model testing CRF effects on Tc function was significant (R2 = .233, F(1, 21) = 7.684, p = .011), where VO2max significantly predicted the change in IFN-γ pre to post stimulation (B = 0.912, p = .011). Regression models testing CRF effects on Tc mitochondrial dependence and glycolytic capacity were significant: both (R2 = .334, F(1,26) = 13.026, p = .001; B = 0.992, p = .001). CRF did not significantly predict Tc glucose dependence or fatty acid/amino acid oxidation (p > .05). CONCLUSION: Individuals with higher CRF had higher Tc function, as indicated by IFN-γ response to stimulation. Higher CRF was also associated with higher Tc oxidative phosphorylation (mitochondrial dependence) and higher capacity to sustain protein synthesis when oxidative phosphorylation was inhibited (glycolytic capacity). These results underscore the potential immune benefits of higher CRF.