title: In vivo expression of B:9-23 peptide/I-A(g7) complex may abrogate the inhibition of diabetes induced by RGD-fiber-mutant adenovirus in NOD mice.
abstract: Insulin B chain peptide B:9-23 given to NOD mice decreases the development of diabetes, and phase II trials of an altered peptide ligand of B:9-23 are under way in humans. We have created a gene for the NOD MHC class II beta chain, covalently linked to the B:9-23 peptide. B lymphoma cells transfected with the gene stimulated NOD islet-derived B:9-23 reactive T cell clones in vitro. In this study, we generated an RGD-fiber-mutant adenovirus vector encoding the covalent B:9-23 peptide/I-A(g7) gene (Ad-RGD-B:9-23) to test whether in vivo expression of the gene could protect NOD mice from diabetes. NOD female mice were injected intramuscularly with 5 x 10(8) PFU of Ad-RGD-B:9-23 and empty RGD-adenovirus vector. A single administration of the empty vector did not alter the expression of insulin autoantibodies, but delayed the onset of diabetes in NOD mice. In contrast, Ad-RGD-B:9-23 immunization induced an early expression of insulin autoantibodies, but did not change the disease occurrence compared to control NOD mice. Our results suggest that adenovirus infection could confer protection from diabetes in NOD mice. The in vivo expression of covalent B:9-23 peptide/class II complex by adenovirus gene transfer might activate anti-insulin autoimmunity, resulting in abrogation of the inhibition of diabetes induced by an RGD-fiber-mutant adenovirus vector.
authors.affiliation: Unit of Metabolism/Diabetes and Clinical Nutrition, Nagasaki University School of Medicine, Nagasaki, Japan.
authors.forename: Norio
authors.initials: N
authors.lastname: Abiru
authors.forename: Fuyan
authors.initials: F
authors.lastname: Sun
authors.forename: Eiji
authors.initials: E
authors.lastname: Kawasaki
authors.forename: Hironori
authors.initials: H
authors.lastname: Yamasaki
authors.forename: Katsuya
authors.initials: K
authors.lastname: Oshima
authors.forename: Yuji
authors.initials: Y
authors.lastname: Nagayama
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Mizuguchi
authors.forename: Takao
authors.initials: T
authors.lastname: Hayakawa
authors.forename: Dongmei
authors.initials: D
authors.lastname: Miao
authors.forename: Edwin
authors.initials: E
authors.lastname: Liu
authors.forename: George S
authors.initials: GS
authors.lastname: Eisenbarth
authors.forename: Katsumi
authors.initials: K
authors.lastname: Eguchi
mesh_terms: D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D003922:Diabetes Mellitus, Type 1 / Q000378:metabolism* / Q000517:prevention & control; D000949:Histocompatibility Antigens Class II / Q000378:metabolism*; D007328:Insulin / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D009154:Mutation; D009842:Oligopeptides; D010446:Peptide Fragments / Q000378:metabolism*
chemical_list: D000949:Histocompatibility Antigens Class II; C407099:I-A g7 antigen; D007328:Insulin; D009842:Oligopeptides; D010446:Peptide Fragments; C097877:insulin B (9-23); C047981:arginyl-glycyl-aspartic acid