Prevention of spontaneous autoimmune diabetes in NOD mice by transferring in vitro antigen-pulsed syngeneic dendritic cells

To evaluate the effect of antigen-pulsed dendritic cell(DC) transfer on the development of diabetes, 5-week-old female NOD mice received a single iv i njection of splenic syngeneic DC from euglycemic NOD mice pulsed in vitro w ith human gamma globulin (HGG). Eleven of 12 mice were protected from the d evelopment of diabetes up to the age of 25 weeks, and the insulitis score w as significantly reduced. In contrast, NOD mice receiving unpulsed splenic DCs showed histological signs of insulitis and course of type 1 diabetes si milar to untreated NOD mice. Treatment with HGG-pulsed DC was associated wi th profound modifications of cytokine secretory capacities within the islet s. Thus, supernatants of islets from these mice contained increased levels of interleukin (IL)-4, IL-10, and, to a lesser extent, interferon-gamma and diminished levels of tumor necrosis factor-alpha compared with controls. B ecause exogenous IL-4 and IL-10 exert antidiabetogenic effect in NOD mice a nd early blockade of endogenous tumor necrosis factor-a prevents NOD mouse diabetes, these phenomena may be causally related to the antidiabetogenic e ffect of HGG-pulsed DC treatment.