Perivascular tissue resident memory T cells as therapeutic target in multiple sclerosis

Multiple sclerosis (MS) is characterized by inflammatory attacks of infiltrating leukocytes at onset but evolves into a smoldering, progressive disease within the central nervous system at its later stages. The authors discuss the contribution of white matter lesions to the pathology of advanced MS, thereby paying particular attention to the role of T cells.

Diagnostic biopsy and autopsy studies of white matter lesions in early MS show different pathological patterns of demyelination and leukocyte infiltration. Brain autopsies from advanced MS display substantial inflammation without distinct patterns and suggest a role for perivascular CD8⁺ tissue-resident memory T (T_RM) cells in active and mixed active/inactive MS white matter lesions. When compared to control and normal-appearing white matter, these lesions are enriched for parenchymal CD8⁺ T cells. In the perivascular space, cuffs containing CD8⁺ T_RM cells are observed also in progressive MS, and could be sites of local reactivation.

Recent findings point toward the perivascular space as an immunological hotspot, which could be targeted in order to suppress a contribution of T_RM cells to ongoing white matter lesion activity in advanced progressive MS. The authors discuss approaches, which may be explored to suppress T_RM-cell reactivation in the perivascular space.