INTERLEUKIN-4 OR INTERLEUKIN-10 EXPRESSED FROM ADENOVIRUS-TRANSDUCED SYNGENEIC ISLET GRAFTS FAILS TO PREVENT BETA-CELL DESTRUCTION IN DIABETIC NOD MICE

Background. We performed ex vivo adenoviral gene transfer in a mouse p ancreatic islet transplant model to test the efficacy of this expressi on system. We then determined whether adenoviral-mediated expression o f mouse interleukin (IL) 4 or IL-10 from transduced syngeneic islet gr afts could prevent disease recurrence in diabetic nonobese diabetic (N OD) mice. Methods. An adenoviral vector expressing beta-galactosidase (AdCMV beta Gal) was used to transduce BALB/c islets (2.5 x 10(3) plaq ue-forming units/islet), which were analyzed for glucose responsivenes s, islet cell recovery, and efficiency of gene transfer. In vivo funct ion and reporter gene expression were examined with AdCMV beta Gal-tra nsduced islet grafts in alloxan-induced diabetic syngeneic recipients. Adenoviruses expressing either IL-4 or IL-10 were used in a similar f ashion to infect NOD islets, which were characterized in vitro, as wel l as transplanted into diabetic syngeneic recipients. Results. In vitr o functional studies showed no significant difference between control or transduced islets, with 50 +/- 4% of AdCMV beta Gal-infected islet cells staining positive for beta-galactosidase, Transplant recipients became nomoglycemic within 48 hr after transplant, and, although beta- galactosidase expression decreased over time, it was detectable in the graft for up to 8 weeks. Despite the nanogram quantities of IL-4 or I L-10 produced/day from each graft equivalent in vitro, transduced and transplanted NOD islets failed to prevent disease recurrence. Conclusi ons. These results suggest that adenoviruses are efficient for at leas t medium term gene expression from islets in vivo, but neither IL-4 no r IL-10 alone can prevent autoimmune disease recurrence in NOD mice.