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

Diabetes
S EfratM S Horwitz

Abstract

The early three (E3) region of the adenovirus (Ad) encodes a number of immunomodulatory proteins that interfere with class I major histocompatibility-mediated antigen presentation and confer resistance to cytokine-induced apoptosis 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 diabetic (NOD) mice decreases the incidence and delays the onset of autoimmune diabetes. The immune effector cells of RIP-E3/NOD mice maintain the ability to infiltrate the islets and transfer diabetes into NOD-scid recipients, although at a significantly reduced rate compared with wild-type littermates. The islets of RIP-E3/ NOD mice can be destroyed by adoptive transfer of splenocytes from wild-type NOD mice; however, the time to onset of hyperglycemia is delayed significantly, and 40% of these recipients were 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.

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Citations

Dec 18, 2001·Diabetes/metabolism Research and Reviews·B NazlielB Koçer
Sep 26, 2002·Virus Research·Adrienne L McNees, Linda R Gooding
Jul 13, 2002·Trends in Molecular Medicine·Shimon Efrat
Nov 21, 2009·Cell Death and Differentiation·H E ThomasT W H Kay
Nov 11, 2005·American Journal of Therapeutics·Nick Giannoukakis, Massimo Trucco
Jul 23, 2002·Journal of Virology·Alexander M LesokhinMarshall S Horwitz
Jun 27, 2002·American Journal of Pharmacogenomics : Genomics-related Research in Drug Development and Clinical Practice·Shimon Efrat
Dec 24, 2003·International Reviews of Immunology·Drew L LichtensteinWilliam S M Wold
Nov 21, 2007·Advanced Drug Delivery Reviews·Shimon Efrat
Feb 28, 2007·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Elena V MashalovaMarshall S Horwitz
May 7, 2003·Gene Therapy·R BottinoN Giannoukakis
Apr 22, 2004·The Journal of Immunology : Official Journal of the American Association of Immunologists·Mark M W ChongHelen E Thomas

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