Effects of lactate concentration on T-cell phenotype and mitochondrial respiration

Lactate is a critical regulator of cellular processes and immune signaling, and we hypothesize that exercise-induced elevations in lactate help activate immune cells in response to vigorous exercise. Despite its importance, the impact of lactate on T-cell mitochondrial respiration remains poorly understood. This study examines the impact of exposure to physiologically relevant lactate concentrations (0.5 and 4.0 mM) on the mitochondrial respiration of resting T-cells. Resting T-cells were isolated from 12 healthy participants (mean ± SD, 26.8 ± 3.5 years) and cultured in a plasma-like medium with either 0.5 mM (control) or 4 mM lactate for 1 h to mimic resting and vigorous exercise conditions. The composition of T-cell subsets was characterized using flow cytometry, and mitochondrial respiration was measured using high-resolution respirometry. Exposure to 4 mM lactate significantly increased mitochondrial oxygen flow (I_O2, pmols∙s^-1 million T-cells^-1) across all respiratory states compared to the control condition (0.5 mM) (all p < 0.01), suggesting an enhanced capacity for oxidative phosphorylation compared to the control. This study demonstrates that lactate preconditions T-cells and leads to enhanced mitochondrial respiration, offering insights into immune cell metabolism under exercise-like conditions, independent of exercise-induced differential mobilization of immune cell subsets.