Adenovirus early region 3 (E3) immunomodulatory genes decrease the incidence of autoimmune diabetes in NOD mice

The early three (E3) region of the adenovirus (Ad) encodes a number of immu nomodulatory proteins that interfere with class I major histocompatibility- mediated antigen presentation and confer resistance to cytokine-induced apo ptosis in cells infected by the virus. Transgenic expression of Ad E3 genes under the rat insulin II promoter (RIP-E3) in beta -cells in nonobese diab etic (NOD) mice decreases the incidence and delays the onset of autoimmune diabetes. The immune effector cells of RTP-E3/NOD mice maintain the ability to infiltrate the islets and transfer diabetes into NOD-scid recipients, a lthough at a significantly reduced rate compared with wild-type littermates . The islets of RIP-E3/NOD mice can be destroyed by adoptive transfer of sp lenocytes from wild-type NOD mice; however, the time to onset of hyperglyce mia is delayed significantly, and 40% of these recipients mere not diabetic at the end of the experiment. These findings suggest that expression of E3 genes in beta -cells affects both the activation of immune effector cells and the intrinsic resistance of beta -cells to autoimmune destruction.