¹Autoimmunity/Diabetes Group, The John P Robarts Research Institute, London, Ontario, Canada

²Department of Microbiology and Immunology, University of Western Ontario, London, Ontario, Canada

³Department of Pathology, McMaster University, Hamilton, Ontario, Canada

⁴Department of Medicine, University of Western Ontario, London, Ontario, Canada

Correspondence to: T L Delovitch, Autoimmunity/Diabetes Group, The John P Robarts Research Institute, 1400 Western Road, London, Ontario N6G 2V4, Canada

We have previously shown that systemic injection of multiple low doses of recombinant murine interleukin-4 (mIL-4) can prevent type 1 diabetes (T1D) 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 mIL-4. We found that only two systemic injections of a recombinant adenovirus type 5 vector-expressing mIL-4 (Ad5mIL-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 Ad5mIL-4 treatment as a possible therapeutic agent against T1D. Thus, adenovirus-mediated delivery of IL-4 provides protection of NOD mice from T1D and represents a clinically viable therapeutic approach. Gene Therapy (2000) 7, 1840-1846.

type 1 diabetes; NOD mice; gene transfer; IL-4; t helper cells