Osteopontin associates with brain T-cell transcriptome and compartmentalization in donors with and without multiple sclerosis.

The human brain is populated by perivascular T cells with a tissue-resident memory T (T)-cell phenotype, which in multiple sclerosis (MS) associate with lesions. We investigated the transcriptional and functional profile of freshly isolated T cells from white and gray matter. RNA sequencing of CD8 and CD4 CD69 T cells revealed T-cell signatures. Notably, gene expression hardly differed between lesional and normal-appearing white matter T cells in MS brains. Genes up-regulated in brain T cells were (CD20) and (osteopontin, OPN). OPN is also abundantly expressed by microglia and has been shown to inhibit T cell activity. In line with their parenchymal localization and the increased presence of OPN in active MS lesions, we noticed a reduced production of inflammatory cytokines IL-2, TNF, and IFNγ by lesion-derived CD8 and CD4 T cells . Our study reports traits of brain T cells and reveals their tight control in MS lesions.