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

Med Sci Sports Exerc. 2024 May 15. doi: 10.1249/MSS.0000000000003483. Online ahead of print.

Abstract

Introduction: The study aimed to investigate to what extent acute endurance exercise, especially eccentric exercise and cardiorespiratory fitness affect the metabolic profile of CD4 + cells.

Methods: 15 male, healthy adults aged between 20 and 33 years with a maximal oxygen uptake (VO 2max ) between 44 and 63 ml/kg/min performed a downhill run (DR) and a level run (LR) for 45 minutes at 70% of their VO 2max on a treadmill in a cross-over design. Blood samples were taken before (T0), directly after (T1), 3 hours after (T3), and 24 hours (T24) after each exercise for analyzing leukocyte numbers and cytokine levels. Isolated CD4 + cells were incubated for 4 hours in autologous resting versus 3 hours 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 < .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 = .617, p = .033) and with gene expression of oxidative phosphorylation and levels of different metabolites. Similarly, VO 2max 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 VO 2max (p < .001).

Conclusions: Acute exercise leads to a mild pro-inflammatory 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.