Altered phenotype and function of blood dendritic cells in multiple sclerosis are modulated by IFN-beta and IL-10

Multiple sclerosis (MS) is assumed to result from autoaggressive T cell-med iated immune responses, in which T helper type 1 (Th1) cells producing cyto kines, e.g. IFN-gamma and lymphotoxin promote damage of oligodendrocyte-mye lin units. Dendritic cells (DCs) as potent antigen presenting cells initiat e and orchestrate immune responses. Whether phenotype and function of DCs w ith respect to Th1 cell promotion are altered in MS, are not known. This st udy revealed that blood-derived DCs from MS patients expressed low levels o f the costimulatory molecule CD86. In addition, production of IFN-gamma by blood mononuclear cells (MNCs) was strongly enhanced by DCs derived from MS patients. IFN-beta and IL-10 inhibited the costimulatory capacity of DCs i n mixed lymphocyte reaction (MLR) and showed additive effects on suppressio n of IL-12 production by DCs. Correspondingly, DCs pretreated with IFN-beta and IL-10 significantly suppressed IFN-gamma production by MNCs. IFN-beta in vitro also upregulated CD80 and, in particular, CD86 expression on DCs. In vitro, anti-CD80 antibody remarkably increased, while anti-CD86 antibody inhibited DC-induced IL-4 production in MLR. We conclude that DC phenotype and function are altered in MS, implying Th1-biased responses with enhance d capacity to induce Th1 cytokine production. In vitro modification of MS p atients' DCs by IFN-beta and IL-10 could represent a novel way of immunomod ulation and of possible usefulness for future immunotherapy of MS.