Respiratory and Metabolic Responses of CD4+ T Cells to Acute Exercise and Their Association with Cardiorespiratory Fitness

Abstract

ABSTRACT Introduction The study aimed to investigate to what extent acute endurance exercise, especially eccentric exercise and cardiorespiratory fitness, affects the metabolic profile of CD4+ cells. Methods Fifteen male, healthy adults aged between 20 and 33 yr with a maximal oxygen uptake (V̇O2max) between 44 and 63 mL·kg−1·min−1 performed a downhill run (DR) and a level run (LR) for 45 min at 70% of their V̇O2max on a treadmill in a crossover design. Blood samples were taken before (T0), directly after (T1), 3 h after (T3), and 24 h (T24) after each exercise for analyzing leukocyte numbers and cytokine levels. Isolated CD4+ cells were incubated for 4 h in autologous resting versus 3 h after exercise serum (T3 DR and T3 LR), and subsequently, cellular respiration, transcriptomic, and metabolomics profiles were measured. Results The systemic immune inflammation index increased significantly after DR and LR at T1 and T3 (P < 0.001). In contrast, the transcriptomic and metabolic profile of CD4+ cells showed no significant alterations after incubation in T3 exercise serum. However, cardiorespiratory fitness positively correlated with the maximal mitochondrial respiration in CD4+ cells after incubation with T3 LR serum (r = 0.617, P = 0.033) and with gene expression of oxidative phosphorylation and levels of different metabolites. Similarly, V̇O2max was associated with an anti-inflammatory profile on RNA level. Lower lactate, methylmalonic acid, and d-gluconic acid levels were found in CD4+ cells of participants with a high V̇O2max (P < 0.001). Conclusions Acute exercise leads to a mild proinflammatory milieu with only small changes in the metabolic homeostasis of CD4+ cells. High cardiorespiratory fitness is associated with a metabolic shift to oxidative phosphorylation in CD4+ cells. Functional relevance of this metabolic shift needs to be further investigated.