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

Eur J Immunol. 2014 Oct;44(10):3119-28. doi: 10.1002/eji.201344160. Epub 2014 Aug 19.


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.

Keywords: CD161; IL-17; IL-18; MAIT cells; Multiple sclerosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • CD8-Positive T-Lymphocytes / immunology*
  • Chemotaxis, Leukocyte
  • Flow Cytometry
  • Humans
  • Immunohistochemistry
  • Interleukin-18 / blood*
  • Lymphocyte Activation / immunology
  • Multiple Sclerosis / blood
  • Multiple Sclerosis / immunology*
  • Multiple Sclerosis / pathology
  • T-Lymphocyte Subsets / immunology*


  • IL18 protein, human
  • Interleukin-18