Brayman K L, Markman J F, Barker C F, Naji A
Department of Surgery, University of Pennsylvania School of Medicine, Philadelphia 19104.
Surgery. 1988 Aug;104(2):445-52.
The autoimmune diabetic syndrome of the biobreeding (BB) rat currently constitutes the best animal model for human type I diabetes. Since prediction of human beings at high risk for development of diabetes by immunologic and physiologic parameters is not possible at present, we investigated the feasibility of immunoprediction of diabetes in normoglycemic BB diabetes-prone (BBdp) rats. Peripheral blood lymphocyte counts (PBLC) accurately predicted future development of diabetes in a cohort of 50 BBdp rats (100% specificity, 95.8% sensitivity for PBLC less than 3800/mm3). We also assessed the fate of normal islets transplanted from MHC-compatible non-diabetes-prone Wistar Furth (WF) donors in the prediabetic milieu of BBdp hosts that were known on the basis of their PBLC destined either to become diabetic or to remain normoglycemic. In 13 BBdp rats in which diabetes was predicted the native pancreatic beta cells were eliminated at 35 days of age with streptozocin and replaced with transplanted WF islets. Neonatally induced tolerance of WF antigens prevented rejection. After successful islet transplantation, spontaneous diabetes occurred in 100% (5/5) of the rats in which the development of diabetes was predicted. The identical protocol in eight rats predicted not to have diabetes resulted in permanent normoglycemia in all. We conclude that normal islets are susceptible to anti-islet autoimmunity after transplantation in the prediabetic period.
生物繁殖（BB）大鼠的自身免疫性糖尿病综合征目前是人类I型糖尿病的最佳动物模型。由于目前无法通过免疫和生理参数预测人类患糖尿病的高风险，我们研究了在血糖正常的BB糖尿病易感性（BBdp）大鼠中进行糖尿病免疫预测的可行性。外周血淋巴细胞计数（PBLC）准确预测了一组50只BBdp大鼠未来的糖尿病发展情况（特异性为100%，PBLC低于3800/mm3时敏感性为95.8%）。我们还评估了从MHC相容的非糖尿病易感性Wistar Furth（WF）供体移植的正常胰岛在BBdp宿主的糖尿病前期环境中的命运，这些宿主根据其PBLC已知要么会患糖尿病，要么会保持血糖正常。在13只预测会患糖尿病的BBdp大鼠中，在35日龄时用链脲佐菌素消除了天然胰腺β细胞，并用移植的WF胰岛替代。新生儿诱导的对WF抗原的耐受性防止了排斥反应。成功进行胰岛移植后，预测会患糖尿病的大鼠中有100%（5/5）出现了自发性糖尿病。在8只预测不会患糖尿病的大鼠中采用相同方案，结果所有大鼠都实现了永久性血糖正常。我们得出结论，在糖尿病前期移植后，正常胰岛易受抗胰岛自身免疫的影响。
