Multiple sclerosis is associated with high levels of circulating dendriticcells secreting pro-inflammatory cytokines

Recent evidence emphasises a pivotal role for dendritic cells (DC)in the co ntrol of immunity by priming and tolerising T cells. DC capture and process antigens, express co-stimulatory molecules, migrate to lymphoid organs and secrete cytokines to initiate immune responses. En multiple sclerosis (MS) , autoreactive T cells are proposed to play a pathogenic role by secreting pro-inflammatory cytokines, but studies on DC are lacking. To evaluate the involvement of DC in patients with MS, a modified procedure was used to pre pare DC from blood of patients with MS and healthy subjects. DC were found to be potent stimulators of T cells in allogeneic and, to a lesser extent, in autologous mixed leukocyte reaction (MLR). Enzyme-linked immunospot (ELI SPOT) assays were adopted to determine levels of IFN-gamma, TNF-alpha , IL- 6 and IL-IO secreting DC vs, mononuclear cells(MNC) Proportionally more DC than MNC secreted IFN-gamma and IL-10 in both MS and healthy subjects. Pati ents with MS had higher levels of IFN-gamma, TNF-alpha and IL-6 secreting D C than healthy subjects. The differences for IFN-gamma and TNF-alpha secret ing cells were confined to the subgroup of untreated MS patients and not ob served in the subgroup examined during ongoing treatment with IFN-beta. Cir culating DC secreting pro-inflammatory cytokines may represent another focu s for the study of both immuno-pathogenesis and therapeutic interventions i n MS. (C) 1999 Elsevier Science B.V All rights reserved.