566. Delaying the Onset of Diabetes in the NOD Mouse Using Exosomes Derived from Dendritic Cells Transfected with Adenoviral Vectors

Exosomes are nanovesicles produced in the late endosome and secreted by various cell types, including dendritic cells (DC) and other antigen presenting cells. Studies of tumor-derived exosomes have demonstrated that they are capable of suppressing host anti- tumor immune response and placental-derived exosomes play an important role in establishing maternal immune tolerance toward the fetus. We have demonstrated previously that exosomes derived from DC transfected with adenoviral vectors containing anti- inflammatory molecules such as IL-10, IL-4 and FasL are capable of suppressing antigen-specific immune responses in multiple disease models, such as delayed type hypersensitivity and collagen-induced arthritis. In this study, we examine the ability of DC and DC-derived exosomes to halt the progression of diabetes in the NOD model of autoimmune diabetes. Exosomes were isolated by differential centrifugation from the enriched culture medium of bone marrow derived DC from NOD/LTJ mice transduced with either an adenoviral vector encoding IL-4 or a control empty vector. NOD/LTJ mice were treated via tail vein injection with either the transduced DC or the exosome preparation. The DC transduced with IL-4 were able to prevent the onset of diabetes with a single treatment to either 5- or 10-week old NOD mice, similar to our previous results. Interesting, treatment of NOD/LTJ with DC-derived exosomes also prevented the onset of hyperglycemia. These results suggest that exosomes from immunosuppressive DC are able to block progression of diabetes in NOD mice and thus could be used clinically to treat type I diabetes.