Molecular Analysis of the Pathogenesis of Autoimmune Insulitis in NOD Mice

Among diabetes-susceptibility genes in NOD mice, only Idd-1 has been clearly assigned: Idd-1 could be a gene complex composed of class II major histocompatibility complex (MHC) genes, I-Aβ and I -E. Employing restriction fragment length polymorphism (RFLP) analysis and nucleotide sequencing, we revealed that ILI and CTS mice, which are nondiabetic but are derived from the same Jcl-ICR mice as NOD mice, share the same class II MHC genes with NOD mice, suggesting that both ILI and CTS mice also possess susceptible Idd-1 genotype. This was supported by a breeding study. To compare the usage of T cell receptor (TCR) Vβ genes in NOD mice with that in ILI mice, we employed quantitative reverse-transcriptase polymerase chain reaction (RT-PCR) which revealed that TCR Vβ usages of these mice were indistinguishable. RT-PCR method also revealed that the Vβ transcript of T cells infiltrating into pancreas of NOD mice was not restricted but was rather diverse. Since NOD and ILI mice share the same class I and II MHC antigens, we performed lymphocyte transfer experiments between these mice to examine the mechanism by which ILI mice do not develop insulitis. The results of reciprocal transfer of lymphocytes from NOD to ILI-nu/nu mice or from ILI to young NOD mice suggest that ILI mice exhibit autoantigens responsible for the development of insulitis but do not possess T cells reacting with islets. Of the diabetes-susceptibility genes, only in the case of Idd-1 is there any evidence for the identity of the gene products. ILI mice should provide more information on the products of the other diabetes-susceptibility genes of NOD mice.rights:東北ジャーナル刊行会rights:本文データは学協会の許諾に基づきJ-STAGEから複製したものであ