CD8+ MAIT cells infiltrate into the CNS and alterations in their blood frequencies correlate with IL‐18 serum levels in multiple sclerosis

Recent findings indicate a pathogenic involvement of IL-17-producing CD8+ T cells in multiple sclerosis (MS). IL-17 production has been attributed to a subset of CD8+ T cells that belong to the mucosal-associated invariant T (MAIT) cell population. Here, we report a reduction of CD8+ MAIT cells in the blood of MS patients compared with healthy individuals, which significantly correlated with IL-18 serum levels in MS patients. In vitro stimulation of peripheral blood mononuclear cells from healthy individuals and MS patients with IL-18 specifically activated CD8+ MAIT cells. Moreover, IL-18 together with T-cell receptor stimulation induced, specifically on CD8+ MAIT cells, an upregulation of the integrin very late antigen-4 that is essential for the infiltration of CD8+ T cells into the CNS. Notably, we were able to identify CD8+ MAIT cells in MS brain lesions by immunohistochemistry while they were almost absent in the cerebrospinal fluid (CSF). In summary, our findings indicate that an IL-18–driven activation of CD8+ MAIT cells contributes to their CNS infiltration in MS, in turn leading to reduced CD8+ MAIT-cell frequencies in the blood. Therefore, CD8+ MAIT cells seem to play a role in the innate arm of immunopathology in MS.