Immunometabolic profiling of T cells in response to prolonged moderate intensity cycling in humans.

Abstract

Background: Emerging data indicates that enrichment of peripheral blood with T lymphocytes during exercise and their associated changes in function are underpinned by modulation of cellular bioenergetics. However, there is a dearth of literature examining these responses using metabolic thresholds to prescribe exercise intensity or providing single cell resolution on immunometabolic outcome measures.

Objectives: The current study was designed to examine the metabolic phenotypes and real-time bioenergetic responses to activation of enriched naïve helper (CD4+) and cytotoxic (CD8+) T cells and peripheral blood mononuclear cells (PBMCs) in response to prolonged cycling.

Methods: Tenaerobically trained males and females (mean ± SD: age 21±1 years; maximal oxygen consumption: 53.9 ± 9.8 ml · kg-1 · min-1) undertook a 2-hour bout of continuous cycling at a power output eliciting 95% lactate threshold-1. Blood samples were collected at rest, immediately (post), and 2 hours after cycling cessation (recovery). Using injection sequences of cell respiration modulators and a CD3/CD28 activator, bioenergetic profiles of PBMCs and enriched naïve CD4+ and CD8+ T cells were determined using extracellular flux analysis. Mitochondrial membrane potential (ΔΨm) was examined using flow cytometry.

Results: Despite cycling evoking significant fluctuations in peripheral blood T cell numbers, there were no changes in absolute or relative measures of mitochondrial respiration, glycolytic flux and ATP synthesis rate post and recovery vs rest. Contribution of mitochondrial respiration to ATP production was greater than glycolysis in naïve T cells across all timepoints, but not PBMCs in recovery. This was despite absolute and relative changes in ΔΨm of memory T cells being greater in recovery vs. rest. Bioenergetic responses to ex vivo T cell activation were not different between cell types or timepoints.

Conclusion: These data indicate that the metabolic phenotypes of naïve T cells and PBMCs were largely unaltered within 2 hours of prolonged moderate intensity cycling.