Abstract
Multiple Sclerosis (MS) represents a neuroinflammatory autoimmune disease characterized by the predominance of circulating T cell subsets with proinflammatory characteristics and increased central nervous system (CNS)-homing potential. Substantial evidence confirms various beneficial effects of chronic exercise interventions in MS, but it is unknown how long-term multi-modal intense exercise affects MS-associated lymphocytes that are commonly targeted by medication in persons with relapsing remitting MS (pwRRMS). A total of 45 participants with defined RRMS were randomized to either the exercise (n=22) or passive waitlist-control group (n=23). A 10-week intervention consisting of progressive resistance and strength-endurance exercises was applied (3x/week à 60min). Blood was drawn before (T1) and after (T2) the intervention period. Flow cytometry was used for phenotyping lymphocyte subsets. Relative protein expression of CD49d within CD8+ T cells, quantified via mean fluorescence intensity (MFI), is significantly associated with the Expanded Disability Status Scale (p=0.007, r=0.440), decreased in the exercise group (p=0.001) only, and was significantly lower in the exercise compared to the control group at T2 (p<0.001). T helper (Th) 17 cell frequency decreased only in the exercise group (p<0.001). CD8+CD20+ T cell frequency was significantly lower in the exercise compared to the control group at T2 (p=0.003), without showing significant time effects. The 10-week multimodal exercise intervention mainly affected circulating T cells harboring a pathophysiological phenotype in MS. The findings of a decreased frequency of pathogenic Th17 cells and the reduced CNS-homing potential of CD8+ T cells, indicated by reduced CD49d MFI, substantiate the positive effects of exercise on cellular biomarkers involved in disease activity and progression in MS. To confirm exercise-mediated beneficial effects on both disease domains, clinical endpoints (i.e., relapse rate, lesion formation, EDSS score) should be assessed together with these cellular and molecular markers in studies with a larger sample size and a duration of six to twelve months or longer.
Published Version
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