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.
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.
Abiru
Norio
N
Unit of Metabolism/Diabetes and Clinical Nutrition, Nagasaki University School of Medicine, Nagasaki, Japan.
Sun
Fuyan
F
Kawasaki
Eiji
E
Yamasaki
Hironori
H
Oshima
Katsuya
K
Nagayama
Yuji
Y
Mizuguchi
Hiroyuki
H
Hayakawa
Takao
T
Miao
Dongmei
D
Liu
Edwin
E
Eisenbarth
George S
GS
Eguchi
Katsumi
K
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*
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