Dysfunction of CD3−CD16+CD56dim and CD3−CD16−CD56bright NK cell subsets in RR-MS patients

Multiple sclerosis (MS), is a chronic inflammatory disease of central nervous system with unclear etiology. Relapsing-remitting (RR)-MS is the most frequent subtype of disease. Natural Killer (NK) cells have roles in cytotoxicity and immune regulation by cytokine secretions, with uncertain contribution to MS pathogenesis. This study aimed to explore contribution of NK cells to MS pathogenesis. Percentages of CD3−CD16+CD56+ total NK cells, CD3−CD16+CD56dim and CD3−CD16−CD56bright NK cell subsets, NK cytotoxicity and intracellular IFN-γ, IL-10 and IL-22 levels were investigated in patients with RR-MS and clinically isolated syndrome (CIS) as well as healthy subjects. Decreased IFN-γ and increased IL-22 production might have detrimental effects on the clinical course of RR-MS. Impaired cytotoxicity is correlated with disease duration in RR-MS. These findings support the possible contribution of NK cells to RR-MS immuno-pathogenesis. •Decreased NK cell frequencies in untreated RR-MS•Impaired NK cell cytotoxicity in RR-MS and CIS, associated with disease durations•Inadequate IFN-g levels in both NK cell subsets of RR-MS and CIS•Increased IL-22 together with impaired IL-22 suppression in response to hrIL-4 in CD3−CD16+CD56dim cells in RR-MS and CIS•IL-10 production of CD3-CD16-CD56bright NK cell subset suppressed by IFN-beta treatment