Project description:CD8+ T cells are the dominant lymphocyte population in multiple sclerosis (MS) lesions where they are highly clonally expanded. The clonal identity, function, and antigen specificity of CD8+ T cells in MS are not well understood. Here we report a comprehensive single-cell RNA-seq and T cell receptor (TCR)-seq analysis of the cerebrospinal fluid (CSF) and blood from a cohort of treatment-naïve MS patients and control participants. A small subset of highly expanded and activated CD8+ T cells were enriched in the CSF in MS that displayed high activation, cytotoxicity and tissue-homing transcriptional profiles. Using a combination of unbiased and targeted antigen discovery approaches, MS-derived CD8+ T cell clonotypes recognizing Epstein-Barr virus (EBV) antigens and multiple novel mimotopes were identified. No CD8+ T cell cross-reactivity was found between the EBV epitopes and self-antigens, but EBV DNA was detected in CSF, including in the same individuals with highly expanded CD8+ T cells. These findings shed vital insight into the role of CD8+ T cells in MS and lend further support an important role of EBV in MS immunopathology.
Project description:We performed gene expression profiling on paired cerebrospinal fluid (CSF) and peripheral blood lymphocyte (PBL) samples from 26 Multiple sclerosis patients without immunomodulatory treatment sampled in relapse or in remission, and 18 controls with other non-inflammatory neurological disorders using Human Genome U133 plus 2.0 arrays (Affymetrix).
