Intrathecally expanded GZMK+/GZMH+ CD8 T cells targeting EBV antigens may reduce severity of Multiple Sclerosis.

ABSTRACT: Combining cerebrospinal fluid B cell receptor and T cell receptor repertoire analysis with transcriptional/ flow cytometry cellular profiles in hundreds of deeply-phenotyped people with Multiple Sclerosis (pwMS) and controls, we identified intrathecal expansion of anti-viral, cytotoxic, granzymes H/K (GZMH+/GZMK+) double positive (DP) CD8+ T cells that recognize EBV epitopes in pwMS. DP CD8+ T cells are activated and expanded by, and kill autologous, EBV-infected CSF B cell lines in-vitro. Correlations of surrogate transcriptional profiles with clinical and imaging outcomes infer a beneficial role for EBV-targeting DP CD8+ T cells, as untreated pwMS with proportionally higher DP CD8+ T cells to intrathecal B cells accumulate neurological disability slower. MS therapies also increase ratios

SUBMITTER: Ashida S 

PROVIDER: S-EPMC12443058 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature