Immunotherapy of spontaneous type I diabetes in nonobese diabetic mice by systemic interleukin-4 treatment employing adenovirus vector-mediated gene transfer

We have previously shown that systemic injection of multiple low doses of recombinant murine interleukin-4 (mlL-4) can prevent type I diabetes (TID) in nonobese diabetic (NOD) mice by activating regulatory T helper (Th) 2 cells in vivo. Here, we have developed a gene transfer approach to the prevention of T1D by testing the therapeutic potential of an adenovirus gene transfer vector engineered to express mlL4. We found that only two systemic injections of a recombinant adenovirus type 5 vector-expressing mlL-4 (Ad5mlL-4) reduces destructive insulitis and protects NOD mice from the onset of diabetes by eliciting intrapancreatic Th2 cell responses. Host immune responses against the adenovirus vector were detectable; however, the levels of antibody production were insufficient to preclude Ad5mlL-4 treatment as a possible therapeutic agent against TID. Thus, adenovirus-mediated delivery of IL-4 provides protection of NOD mice from TID and represents a clinically viable therapeutic approach.