Induction of tolerance by IL-10-treated dendritic cells

Abstract

Dendritic cells (DC) form a specialized system for presenting Ag to naive or quiescent T cells and consequently play a central role in the induction of T and B cell immunity. In this study we used DC generated from peripheral progenitors to analyze the effect of IL-10 on the accessory function of human DC. We demonstrate that immature DC, harvested on days 9 to 11 and exposed to IL-10 for the last 2 days of culture, show a strongly reduced capacity to stimulate a CD4+ T cell response in an allogeneic MLR in a dose-dependent manner. In contrast, fully mature DC are completely resistant to the effects of IL-10. These results were obtained in both an alloantigen-induced MLR and an anti-CD3 mAb-induced response of primed and naive (CD45RA+) CD4+ T cells. FACS analysis revealed inhibition of the up-regulation of the costimulatory molecules CD58 and CD86 and the specific DC marker CD83 in DC pretreated with IL-10. These data suggest that IL-10 inhibited the development of fully mature DC. Furthermore, DC precultured with IL-10, but not controls, induced a state of alloantigen-specific anergy in CD4+ T cells and of peptide-specific anergy in the influenza hemagglutinin-specific T cell clone HA1.7. Analysis of the supernatants of these anergic T cells revealed a reduced production of IL-2 and IFN-gamma compared with that in control cells. Collectively, these data suggest that IL-10 converts immature DC into tolerogenic APC, which might be a useful tool in the therapy of patients with autoimmune or allergic diseases.