Purpose: Chronic exercise training is known to induce metabolic changes, but whether these adaptations extend to lymphocytes and how this may affect immune function remains largely unknown. This study was conducted to determine the extent to which mitochondrial characteristics of naïve T cells differ according to fitness status and to further examine the energy production pathways of cells from aerobically trained and inactive participants.

Methods: Blood was collected from 30 aerobically active (>6 h·wk -1 ) or inactive (<90 min·wk -1 ) men and women. Naïve T cell mitochondrial mass, membrane potential, and biogenesis were assessed with flow cytometry. Participants completed a treadmill maximal oxygen consumption (V̇O 2peak ) test and wore a physical activity monitor for 1 wk. In a subset of participants, naïve CD8 + T cell activation-induced glycolytic and mitochondrial ATP production was measured.

Results: Active participants exhibited 16.7% more naïve CD8 + T cell mitochondrial mass ( P = 0.046), 34% greater daily energy expenditure ( P < 0.001), and 39.6% higher relative V̇O 2peak ( P < 0.001), along with 33.9% lower relative body fatness ( P < 0.001). Among all participants, naïve CD8 + T cell mitochondrial mass was correlated with estimated energy expenditure ( r = 0.36, P = 0.048) and V̇O 2peak ( r = 0.47, P = 0.009). There were no significant differences in ATP production, mitochondrial biogenesis, or mitochondrial membrane potential between active and inactive groups.

Conclusions: This is the first study to examine the effects of aerobic exercise training status on metabolic parameters within human naïve T cells. Findings suggest that mitochondrial adaptations in certain immune cell types are positively associated with aerobic fitness and energy expenditure. This study provides a foundation for future development of prophylactic and therapeutic interventions targeting specific immune cell subsets to improve the immune response and overall health.

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