Physical activity attenuates PD-1/PD-L1 expression and enhances CD4⁺ T-cell function in COPD patients.

Chronic obstructive pulmonary disease (COPD) is characterized by systemic inflammation, immune dysregulation, and T-cell dysfunction. The PD-1/PD-L1 immune checkpoint axis is implicated in immune exhaustion and increased exacerbation risk in COPD. Physical activity (PA) is known to exert anti-inflammatory effects, yet its impact on immune checkpoint regulation remains unclear. We aimed to evaluate the association between PA and PD-1/PD-L1 expression in COPD and assess whether a structured PA intervention modulates this axis and improves T-cell function. Ninety-one patients with stable COPD were classified by baseline physical activity level (PAL) using a multiparametric accelerometer. Plasma PD-1/PD-L1 levels, peripheral blood mononuclear cell expression, and T-cell proliferation were assessed pre-and-post-intervention. Sedentary patients showed elevated plasma PD-1/PD-L1 and increased expression in CD4⁺ T cells and monocytes, correlating inversely with activity and CD4⁺ T-cell proliferation. Following the intervention, patients with improved PAL exhibited significant reductions in PD-1 and enhanced CD4⁺ T-cell proliferation. These effects were not observed in CD8⁺ cells, which responded primarily to PD-1 blockade. Physical activity is associated with lower PD-1/PD-L1 expression and improved CD4⁺ T-cell function in COPD. A structured PA intervention may modulate immune checkpoint pathways, offering a non-pharmacologic strategy to restore immune competence.