title: CD8⁺ MAIT cells infiltrate into the CNS and alterations in their blood frequencies correlate with IL-18 serum levels in multiple sclerosis.
abstract: 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.
authors.affiliation: Institut für Neuroimmunologie und Multiple Sklerose, Zentrum für Molekulare Neurobiologie, Universitätsklinikum Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Anne
authors.initials: A
authors.lastname: Willing
authors.forename: Oliver A
authors.initials: OA
authors.lastname: Leach
authors.forename: Friederike
authors.initials: F
authors.lastname: Ufer
authors.forename: Kathrine E
authors.initials: KE
authors.lastname: Attfield
authors.forename: Karin
authors.initials: K
authors.lastname: Steinbach
authors.forename: Nina
authors.initials: N
authors.lastname: Kursawe
authors.forename: Melanie
authors.initials: M
authors.lastname: Piedavent
authors.forename: Manuel A
authors.initials: MA
authors.lastname: Friese
mesh_terms: D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002634:Chemotaxis, Leukocyte; D005434:Flow Cytometry; D006801:Humans; D007150:Immunohistochemistry; D020382:Interleukin-18 / Q000097:blood*; D008213:Lymphocyte Activation / Q000276:immunology; D009103:Multiple Sclerosis / Q000097:blood / Q000276:immunology* / Q000473:pathology; D016176:T-Lymphocyte Subsets / Q000276:immunology*
chemical_list: C000589760:IL18 protein, human; D020382:Interleukin-18
keywords: CD161; IL-17; IL-18; MAIT cells; Multiple sclerosis