Abstract: Multiple sclerosis (MS) is an inflammatory neurological disease of the central nervous system with a subclinical phase preceding frank neuroinflammation. CD8⁺ T cells are abundant within MS lesions, but their potential role in disease pathology remains unclear. Using high-throughput single-cell RNA sequencing and single-cell T cell receptor analysis, we compared CD8⁺ T cell clones from the blood and cerebrospinal fluid (CSF) of monozygotic twin pairs in which the cotwin had either no or subclinical neuroinflammation (SCNI). We identified peripheral MS-associated immunological and metabolic alterations indicative of an enhanced migratory, proinflammatory, and activated CD8⁺ T cell phenotype, which was also evident in cotwins with SCNI and in an independent validation cohort of people with MS. Together, our in-depth single-cell analysis indicates a disease-driving proinflammatory role of infiltrating CD8⁺ T cells and identifies potential immunological and metabolic therapeutic targets in both prodromal and definitive stages of the disease.

Kavaka V., et al., Twin study identifies early immunological and metabolic dysregulation of CD8⁺ T cells in multiple sclerosis.  Science Immunology 9(99), 27 Sept.2024:    DOI: 10.1126/sciimmunol.adj8094

https://www.science.org/doi/10.1126/sciimmunol.adj8094