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 IFN gamma signaling may distinguish neurosarcoidosis from other neurological disorders.

Automated summary

This study identified a specific CD8 T cell response enriched in the cerebrospinal fluid of neurosarcoidosis patients, which is distinct from the CD4 T cell response observed in pulmonary sarcoidosis. Furthermore, the expression of EBI2, CXCR3, and CXCR4 distinguished two subsets of CD8 T cells. The findings also suggest that IFN gamma signaling may serve as a potential biomarker to differentiate neurosarcoidosis from other neurological disorders.