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To examine the mechanism underlying the preferential CD8⁺ vs CD4⁺ T-cell lymphopenia induced by dimethyl fumarate (DMF) treatment of MS.

Total lymphocyte counts and comprehensive T-cell subset analyses were performed in high-quality samples obtained from patients with MS prior to and serially following DMF treatment initiation. Random coefficient mixed-effects analysis was used to model the trajectory of T-cell subset losses in vivo. Survival and apoptosis of distinct T-cell subsets were assessed following in vitro exposure to DMF.

Best-fit modeling indicated that the DMF-induced preferential reductions in CD8⁺ vs CD4⁺ T-cell counts nonetheless followed similar depletion kinetics, suggesting a similar rather than distinct mechanism involved in losses of both the CD8⁺ and CD4⁺ T cells. In vitro, DMF exposure resulted in dose-dependent reductions in T-cell survival, which were …