Immune mechanisms in multiple sclerosis: CD3 levels on CD28+ CD4+ T cells link antibody responses to human herpesvirus 6

Compelling evidence suggests a significant association between antibody-mediated immune responses and multiple sclerosis (MS). However, the exact causal relationships between these immune responses and MS remain unclear. In this study, we conducted a comprehensive examination of the link between antibody-mediated immune responses and MS via Mendelian randomization (MR) analysis to identify specific infectious pathogens potentially involved in the onset and progression of MS. We compared immune cell infiltration between MS patients and control subjects. Furthermore, single-cell sequencing was employed to conduct a comparative analysis of the marker genes associated with each cell subtype between individuals diagnosed with MS and the control cohort. We revealed connections between antibody-mediated immune responses and immune cells, as well as the associations between these immune cells and MS. We discovered that CD3 levels on CD28⁺ CD4⁺ T cells significantly influence MS progression by altering the ratio of human herpesvirus 6 (HHV-6). These findings provide novel insights into the biological mechanisms underlying HHV–6–mediated MS.