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 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.
Efrat
S
S
Department of Human Genetics and Molecular Medicine, Sackler School of Medicine, Tel Aviv University, Israel.
Serreze
D
D
Svetlanov
A
A
Post
C M
CM
Johnson
E A
EA
Herold
K
K
Horwitz
M
M
D000256:Adenoviridae / Q000235:genetics*; D017503:Adenovirus E3 Proteins / Q000235:genetics* / Q000276:immunology; D019264:Adoptive Transfer; D000375:Aging; D000818:Animals; D003433:Crosses, Genetic; D003922:Diabetes Mellitus, Type 1 / Q000453:epidemiology / Q000235:genetics* / Q000276:immunology*; D005260:Female; D015994:Incidence; D007328:Insulin / Q000235:genetics; D007515:Islets of Langerhans / Q000276:immunology / Q000473:pathology; D017710:Lymphocyte Transfusion; D051379:Mice; D016688:Mice, Inbred NOD; D008815:Mice, Inbred Strains; D016513:Mice, SCID; D008822:Mice, Transgenic; D011401:Promoter Regions, Genetic; D051381:Rats; D013154:Spleen / Q000276:immunology
D017503:Adenovirus E3 Proteins; D007328:Insulin