Single-cell analysis suggests coordinated immune-cell redistribution between blood and cerebrospinal fluid in early multiple sclerosis

Abstract

Despite immune-cell infiltration being a hallmark of multiple sclerosis (MS), the interplay between the periphery and central nervous system immune responses is still incompletely characterized. We performed single-cell transcriptomic and V(D)J sequencing of paired blood and cerebrospinal fluid (CSF) immune cells from treatment-naive relapsing-remitting women with MS and compared them to age- and sex-matched healthy controls. Across major immune lineages, we identified coordinated, compartment-specific immune alterations, with enrichment of activated and memory lymphocyte populations in the CSF and concomitant depletion of related populations in peripheral blood, suggesting their recruitment from blood to CSF. Clonally expanded CD4 memory T-cells, together with activated, expanded IgM-positive B-cells, accumulated predominantly in the CSF of people with MS compared to healthy subjects. Interestingly, tissue-primed cytotoxic populations and CXCR3-associated memory populations were depleted from the CSF of MS, implying their recruitment to the target tissue in early disease. These findings reveal coordinated, compartment-specific immune changes in early MS and provide a systems-level view of immune-cell trafficking between peripheral and central nervous system compartments.