GEOapplication/xmlftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE308nnn/GSE308973/primaryOK200TranscriptomicsHomo sapiensExpression profiling by high throughput sequencinghttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE308973GEOGSEfalseLocalized PD-1 CAR T therapy reprograms neuroinflammation - human CSF data.B cell-depleting therapies are effective in multiple sclerosis (MS), yet many patients progress toward disability, highlighting the need for improved interventions. To identify new therapeutic targets, we generated a single-cell RNA-seq atlas of cerebrospinal fluid (CSF), brain, and blood from non-inflammatory controls and patients with MS or other neuroinflammatory diseases. We found disease-associated enrichment of class-switched IgG⁺ B cells and plasma cells in the CSF of patients with MS. Unbiased analysis revealed a rare subset of activated PD-1⁺, TCR-restricted, B-cell recruiting T follicular helper-like cells enriched in MS CSF. To therapeutically target this population, we developed PD-1-directed CAR T cells that selectively depleted pathogenic PD-1⁺ CD4 T cells. In a murine model of neuroinflammation, this approach attenuated CNS inflammation and improved clinical outcomes, particularly when using an IL-10-armored CAR construct. These findings establish a cellular framework for CNS-localized adaptive immunity in MS and outline a strategy for its selective disruption.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 sapiens