Abstract
OBJECTIVE: CD8(+) T cells are the most prevailing lymphocyte population in inflammatory lesions of patients with multiple sclerosis (MS) but it is not even known whether they are merely passive bystanders or actively communicate with other cells in the brain. To identify their potential interaction partners, we analyzed CD8(+) T cells that contained vectorially oriented cytotoxic granules and analyzed the areas to which the granules pointed. METHODS: We stained cryo-sections of active MS lesions of an index patient with antibodies to CD8 and perforin, searched for vectorially oriented perforin granules, and isolated target areas opposing the granules and control areas by laser-microdissection. From both areas, we analyzed cell-type specific transcripts by next-generation sequencing. In parallel, we stained samples from the index-patient and other patients by four-color immunohistochemistry (IHC). RESULTS: We found transcripts of the mononuclear phagocyte (MP) specific markers CD163 and CD11b only in the microdissected target areas but not in control areas. We validated the finding that MPs are communication partners of CD8(+) T cells in MS lesions by classical IHC in samples from the index-patient and other patients with acute and progressive MS and other inflammatory neurological diseases. INTERPRETATION: Because CD163 and CD11b are specifically expressed in MPs, our findings suggest that CD8(+) T cells communicate with local MPs. Although it is still unclear if these interactions lead to killing of the communication partners by CD8(+) T cells, our data underline that CD8(+) T cells play an active role in the pathogenesis of MS.