The CSF in neurosarcoidosis contains consistent clonal expansion of CD8 T cells, but not CD4 T cells

The tissue-specific drivers of neurosarcoidosis remain poorly defined. To identify cerebrospinal fluid (CSF) specific, antigen-driven T and B cell responses, we performed single-cell RNA sequencing of CSF and blood cells from neurosarcoid participants coupled to T and B cell receptor sequencing. In contrast to pulmonary sarcoidosis, which is driven by CD4 T cells, we found CD8 T cell clonal expansion enriched in the neurosarcoid CSF. These CSF-enriched CD8 T cells were composed of two subsets with differential expression of EBI2, CXCR3, and CXCR4. Lastly, our data suggest that IFNγ signaling may distinguish neurosarcoidosis from other neurological disorders. [Display omitted] •The CSF from neurosarcoidosis contains consistent clonal expansion of CD8 T cells, but not CD4 T cells.•CSF-enriched CD8 T cell clones express CD27, EBI2, and Granzyme K in both the CSF and the blood.•An interferon signature marks CSF CD8 T cells in neurosarcoidosis.•Elevated CSF levels of IFNγ distinguish active neurosarcoidosis from other CNS disorders.