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 r ecombinant murine interleukin-4 (mlL-4) can prevent type I diabetes (TID) i n nonobese diabetic (NOD) mice by activating regulatory T helper (Th) 2 cel ls in vivo. Here, we have developed a gene transfer approach to the prevent ion of T1D by testing the therapeutic potential of an adenovirus gene trans fer vector engineered to express mlL4. We found that only two systemic inje ctions of a recombinant adenovirus type 5 vector-expressing mlL-4 (Ad5mlL-4 ) reduces destructive insulitis and protects NOD mice from the onset of dia betes by eliciting intrapancreatic Th2 cell responses. Host immune response s against the adenovirus vector were detectable; however, the levels of ant ibody production were insufficient to preclude Ad5mlL-4 treatment as a poss ible therapeutic agent against TID. Thus, adenovirus-mediated delivery of I L-4 provides protection of NOD mice from TID and represents a clinically vi able therapeutic approach.