目的研究非肥胖糖尿病(NOD)鼠是否带有致糖尿病的T细胞及其致糖尿病能力是否随着NOD鼠年龄增长而增加。方法用NOD鼠和NOD背景的转基因鼠为动物模型,通过过继转移将不同周龄的NOD鼠T细胞转移到T细胞缺陷的NOD鼠(即NOD.scid鼠)和在β细胞上表达共刺激分子CD80的NOD.scid鼠(即NOD.scid.Rip.B7鼠)。观察过继转移后诱导受鼠糖尿病的发病率及各受鼠组发病率。结果 (1)80%的NOD.scid.Rip.B7鼠在转移脾细胞11 w后发生糖尿病,而NOD.scid受鼠在转移后20 w尚没有1例受鼠发生糖尿病;(2)在转移后同一时间,不同周龄的NOD供鼠在相同受鼠中诱导的糖尿病发病率差异显著(P<0.001);不同周龄的受鼠糖尿病发病率无统计学差异(P>0.05)。结论 (1)幼年NOD鼠的胰岛没有淋巴细胞浸润是因为β细胞特异性的T细胞数有限,其致糖尿病能力随着NOD供体鼠年龄的增长而增加;(2)在胰岛炎启动前,新生的和幼年的NOD.scid鼠就已经表达与疾病有关的β细胞自身抗原。
Objective To investigate whether young non-obese diabetic ( NOD) mice contain diabetogenic T lymphocytes and the di-abetogenic capacity of T cells increased with the age of NOD mice .Methods NOD mice and NOD background transgenic mice using genetic engineering were used as animal models .According to adoptive transferred experiments , T cells were transferred from NOD mice and NOD background mice to T cell-deficient NOD mice and T cell-deficient NOD mice with co-stimulating molecules CD 80 expressed specific on isletsβcells.The incidence of induced diabetes were investigated in the two recipients .Results Diabetes was induced in 80% of NOD.scid.Rip.B7 mice by 11 weeks post-transfer.In contrast ,none of the NOD.scid recipients developed diabetes even by 20 weeks post-transfer.There was significant difference among the diabetes incidence induced by different age of NOD donor mice by the same time post -transfer(P<0.001).There was no significant difference among different age of recipient mice of the diabetes incidence induced by diabetic NOD donor mice by the same time post-transfer(P>0.05).Conclusions Spleen cells of young NOD mice contain beta cell-specific T cells, however ,the T cell repertoire and/or frequency of diabetogenic T cells are limited .The diabetogenic capacity of T cells is increased with the age of NOD mice.Beta cell antigens have been expressed in young NOD mice before starting the insulitis .