Yasunami R, Bach J F
INSERM U 25-CNRS UA 122-Hôpital, Necker, Paris.
Eur J Immunol. 1988 Mar;18(3):481-4. doi: 10.1002/eji.1830180325.
In the NOD mouse, an autoimmune process beginning by 5 weeks of age with lymphocyte infiltration and destruction of insulin-secreting beta cells leads to overt diabetes which begins to appear by 11 weeks of age. Although there is a high incidence of insulitis by 10 weeks of age (greater than 80%) in both males and females, by 30 weeks of age diabetic symptoms have occurred in 53-80% of females and in 12-40% of males. Intraperitoneal injection of a high dose (200 mg/kg) of cyclophosphamide (CY) consistently induces the onset of diabetes in male and female NOD mice at an age when spontaneous diabetes rarely occurs. Spleen T cells from CY-induced diabetic mice are capable of transferring the disease into irradiated nondiabetic syngeneic recipients. This indicates that the diabetogenic effect of CY is not mediated by direct toxicity on pancreatic beta cells but is mediated by abrogation of a suppressor mechanism which may prevent activation of T cells responsible for the development of diabetes in the NOD mouse. Additionally, CY is only effective in NOD mice and not in F1 hybrids between NOD and other strains of mice. Thus, the potential beta cell aggressor mechanism is not present in these hybrids as it is in homozygous mice, which indicates that it is not under the control of dominant genes.
在非肥胖糖尿病（NOD）小鼠中，5周龄时开始的自身免疫过程，伴有淋巴细胞浸润和胰岛素分泌β细胞的破坏，会导致明显的糖尿病，11周龄时开始出现。尽管10周龄时两性的胰岛炎发病率都很高（超过80%），但到30周龄时，53 - 80%的雌性小鼠和12 - 40%的雄性小鼠出现了糖尿病症状。腹腔注射高剂量（200 mg/kg）的环磷酰胺（CY）能持续诱导雄性和雌性NOD小鼠在很少自发发生糖尿病的年龄发病。CY诱导糖尿病小鼠的脾T细胞能够将疾病转移给经辐射的同基因非糖尿病受体。这表明CY的致糖尿病作用不是由对胰腺β细胞的直接毒性介导的，而是由一种抑制机制的消除介导的，这种抑制机制可能会阻止负责NOD小鼠糖尿病发展的T细胞的激活。此外，CY仅在NOD小鼠中有效，在NOD与其他品系小鼠的F1杂交种中无效。因此，潜在的β细胞攻击机制在这些杂交种中不存在，而在纯合小鼠中存在，这表明它不受显性基因的控制。
