ANTI-CD20 AGENTS RESHAPE THE PHENOTYPE AND FUNCTIONS OF CYTOTOXIC LYMPHOCYTES AND SELECTIVELY MITIGATE EBV-SPECIFIC CD8+ T CELL REACTIVITY IN PEOPLE WITH RELAPSING MULTIPLE SCLEROSIS

Anti-CD20 therapy with ocrelizumab is highly effective in relapsing multiple sclerosis (RMS), but its mechanisms extend beyond B-cell depletion. In a prospective study of 41 RMS patients, we longitudinally assessed CD8+ T cells and NK cells using flow cytometry and functional assays. Ocrelizumab shifted CD8+ T cells toward a naïve phenotype, reduced activation, migratory markers, cytotoxic molecules, and impaired cytotoxic function. NK-cell cytotoxicity was also reduced. Notably, proliferation of EBV-specific CD8+ T cells was selectively decreased, while responses to other viral antigens were preserved. These findings indicate that anti-CD20 therapy reshapes cytotoxic immunity and selectively attenuates EBV-driven responses in RMS.