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

S Efrat·D Serreze·A Svetlanov·C M Post·E A Johnson·K Herold·M Horwitz
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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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AdenoviridaeAdenovirus E3 ProteinsAdoptive TransferAgingAnimalsCrosses, GeneticDiabetes Mellitus, Type 1FemaleIncidenceInsulinIslets of LangerhansLymphocyte TransfusionMiceMice, Inbred NODMice, Inbred StrainsMice, SCIDMice, TransgenicPromoter Regions, GeneticRatsSpleenJournal ArticleResearch Support, Non-U.S. Gov'tResearch Support, U.S. Gov't, P.H.S.

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S Efrat, D Serreze, A Svetlanov, C M Post, E A Johnson, K Herold, M Horwitz. 2001. Adenovirus early region 3(E3) immunomodulatory genes decrease the incidence of autoimmune diabetes in NOD mice.. https://doi.org/10.2337/diabetes.50.5.980

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