GAD65 and insulin B chain peptide (9-23) are not primary autoantigens in the type 1 diabetes syndrome of the BB rat.
To investigate whether GAD65 whole molecule, GAD65 p35 or insulin B chain peptide (amino acids 9-23) play an essential role in the pathogenesis of type 1 diabetes in the BioBreeding (BB) rat, we gave serial injections of GAD65, p35 or insulin B chain (9-23) to six groups of BB/Worcester rats. The individual antigens were administered either intrathymically on day 2 and intraperitoneally in MF 59-0 adjuvant 5 times during the first 5 weeks, or by intranasal instillation once neonatally and 5 days/week for the following 6 weeks. Control groups were injected with vehicle only. Age of onset of diabetes and degree of insulitis were not different between controls and antigen-treated rats. Rats that received GAD65 intrathymically and intraperitoneally developed high GAD65-antibody titers without altering diabetes development. In GAD65-treated animals, serum antibodies recognized epitopes at 3 sites on GAD65 in diabetic animals but only at 1 site in non-diabetic animals. GAD65-injected animals also showed a significant reduction of IFN-gamma mRNA expression in the thymus. This study provides evidence against the hypothesis that GAD65 and insulin B chain peptide (9-23) are primary diabetogenic autoantigens in BB rats because immunizations with these antigens and GAD65-induced immune deviation did not alter the development of diabetes.
Bieg
S
S
Department of Medicine, University of Washington, USA.
Hanlon
C
C
Hampe
C S
CS
Benjamin
D
D
Mahoney
C P
CP
D017668:Age of Onset; D000818:Animals; D000906:Antibodies / Q000097:blood; D001323:Autoantibodies / Q000097:blood; D001324:Autoantigens / Q000276:immunology*; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology* / Q000473:pathology; D005968:Glutamate Decarboxylase / Q000008:administration & dosage / Q000276:immunology*; D006801:Humans; D007091:Image Processing, Computer-Assisted; D007114:Immunization; D017403:In Situ Hybridization; D007328:Insulin / Q000008:administration & dosage / Q000276:immunology*; D007527:Isoenzymes / Q000008:administration & dosage / Q000276:immunology*; D010446:Peptide Fragments / Q000008:administration & dosage / Q000276:immunology*; D011863:Radioimmunoassay; D051381:Rats; D011913:Rats, Inbred BB; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000276:immunology; D013950:Thymus Gland / Q000276:immunology
D000906:Antibodies; D001323:Autoantibodies; D001324:Autoantigens; D016207:Cytokines; D007328:Insulin; D007527:Isoenzymes; D010446:Peptide Fragments; D011994:Recombinant Proteins; C097877:insulin B (9-23); D005968:Glutamate Decarboxylase; C401141:glutamate decarboxylase 2