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

The human brain is populated by perivascular T cells with a tissue-resident mem-ory T (T-RM)-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-RM-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-RM cells were MS4A1(CD20) and SPP1 (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 pres-ence of OPN in active MS lesions, we noticed a reduced production of inflamma-tory cytokines IL-2, TNF, and IFNg by lesion-derived CD8(+) and CD4(+) T cells ex vivo. Our study reports traits of brain TRM cells and reveals their tight control in MS lesions.

Automated summary

The T cells in the human brain have a tissue-resident memory T (T-RM) cell phenotype, which is associated with lesions in multiple sclerosis (MS). Our study investigated the transcriptional and functional profile of T cells from white and gray matter. We found that the gene expression hardly differed between lesional and normal-appearing white matter T cells in MS brains. The up-regulated genes in brain T-RM cells included CD20 and osteopontin, which has been shown to inhibit T cell activity.