Mitochondrial Characteristics Of Adaptive Immune Cells Associated With Aerobic Fitness

Abstract

Recent findings in immunometabolism have demonstrated that the function of immune cells is largely dictated by their metabolism, with mitochondrial characteristics reflecting distinct metabolic phenotypes. A limitation of previous exercise immunology studies is the failure to describe the effect of exercise on specific immune cell subsets. Since exercise may have differential effects that vary by cell population according to metabolic phenotype, analyzing peripheral blood mononuclear cells as a whole may mask adaptations. PURPOSE: To determine the effect of aerobic training on mitochondrial characteristics of specific T cell subsets. METHODS: Non-smokers who self-identified as either completing more than six hours of aerobic-type exercise (ACTIVE) or less than 90 minutes of any type of physical activity (INACTIVE) per week were recruited. Blood was collected and participants returned for a later visit to complete a treadmill maximal oxygen consumption (VO2max) test. Mitochondrial mass and membrane potential (MMP) of CD4+ and CD8+ naïve (CD45RA+ CCR7+) and effector memory (CD45RO+ CCR7-) cells were assessed by geometric mean fluorescence intensity (gMFI) of MitoTracker Green FM and TMRE, respectively. RESULTS: Preliminary statistical analyses (n = 11 each group) revealed that ACTIVE had higher cardiorespiratory fitness than INACTIVE (60.0 ± 9.9 vs. 43.6 ± 8.2 mL/kg/min relative VO2max; p = 0.0004, independent t-test). There were no differences in cell counts between ACTIVE and INACTIVE T cell subsets. Although gMFI indicating mitochondrial mass of CD8+ naïve T cells approached significance between groups (594.7 ± 127.7 ACTIVE vs. 495.4 ± 70.9 INACTIVE; p = 0.0355, independent t-tests), this difference was not statistically significant after correcting for multiple comparisons. Mitochondrial mass and MMP of CD8+ naïve T cells were, however, significantly correlated with relative VO2max (r = 0.5375 and 0.5343, p = 0.0099 and 0.0104, respectively, Pearson correlation). CONCLUSION: These preliminary data suggest that mitochondrial adaptations in certain adaptive immune cells may be associated with aerobic fitness and lay the groundwork for follow-up studies to directly evaluate differences in cellular respiration of these subsets. Funding provided by the ACSM NASA Space Physiology Research Grant.