Koide Y, Kaidoh T, Nakamura M, Yoshida T O
Department of Microbiology/Immunology, Hamamatsu University School of Medicine, Japan.
Tohoku J Exp Med. 1994 May;173(1):157-70. doi: 10.1620/tjem.173.157.
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-A beta 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) V beta genes in NOD mice with that in ILI mice, we employed quantitative reverse-transcriptase polymerase chain reaction (RT-PCR) which revealed that TCR V beta usages of these mice were indistinguishable. RT-PCR method also revealed that the V beta 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.
在非肥胖糖尿病（NOD）小鼠的糖尿病易感基因中，只有Idd-1已被明确确定：Idd-1可能是一个由II类主要组织相容性复合体（MHC）基因I-Aβ和I-E组成的基因复合体。利用限制性片段长度多态性（RFLP）分析和核苷酸测序，我们发现ILI和CTS小鼠虽然不患糖尿病，但与NOD小鼠一样都源自相同的Jcl-ICR小鼠，它们与NOD小鼠共享相同的II类MHC基因，这表明ILI和CTS小鼠也都具有易感的Idd-1基因型。一项育种研究支持了这一结论。为了比较NOD小鼠和ILI小鼠中T细胞受体（TCR）Vβ基因的使用情况，我们采用了定量逆转录聚合酶链反应（RT-PCR），结果显示这些小鼠的TCR Vβ使用情况无法区分。RT-PCR方法还显示，浸润到NOD小鼠胰腺中的T细胞的Vβ转录本不受限制，而是相当多样。由于NOD和ILI小鼠共享相同的I类和II类MHC抗原，我们在这些小鼠之间进行了淋巴细胞转移实验，以研究ILI小鼠不发生胰岛炎的机制。将淋巴细胞从NOD小鼠转移到ILI-nu/nu小鼠或从ILI小鼠转移到年轻NOD小鼠的双向转移实验结果表明，ILI小鼠表现出对胰岛炎发展起作用的自身抗原，但不具有与胰岛反应的T细胞。在糖尿病易感基因中，只有在Idd-1的情况下有证据表明基因产物相同。ILI小鼠应该能提供更多关于NOD小鼠其他糖尿病易感基因产物的信息。
