Horváth M, Varsányi M, Bándi E, Balázsi I, Romics L
3rd Department of Medicine, Semmelweis Medical University, Budapest/Hungary.
Exp Clin Endocrinol. 1992;100(3):90-4. doi: 10.1055/s-0029-1211184.
Previously both specific and nonspecific immune reactions have been reported in patients with type I diabetes mellitus. In this study the effect of various immunosuppressive drugs and insulin was studied on in vitro lymphocyte-mediated cytotoxicity in 20 type I diabetic patients. Twenty sex- and age-matched healthy subjects served as controls. Human pancreas-extract (300 micrograms/ml protein)-coated, 51-Chromium labeled chicken erythrocytes were used as target cells and separated T-lymphocytes as effector cells with and without azathioprine 50 micrograms/50 microliters (Wellcome), Cyclosporine A 5 ng/50 microliters (Sandoz) and MC Actrapid insulin 0.1 IU/50 microliters (Novo). The degree of cytotoxicity was expressed with cytotoxic capacity: the number of maximal killed target cells. Simultaneously islet cell antibodies (ICA) in sera and the number of activated T-lymphocytes were assessed. Significant lymphocyte-mediated cytotoxicity was observed in the majority of type I diabetic patients (18/20), while no cytotoxicity was found in the control cases. The cytotoxicity decreased in all 16 patients using azathioprine or insulin, independently of ICA and HLA-DR positivity. The number of killed target cells was lowered considerably by Cyclosporine A in all 18 patients having cytotoxicity against pancreas-extract. Our observations reveal that Cyclosporine A proved to be the most effective immunosuppressive agent in vitro. It decreases not only the leucocyte migration inhibition as previously observed, but also the lymphocyte-mediated cytotoxicity, which represents the late stage of cellular immune reactions against pancreatic tissue.
此前已有报道称，I型糖尿病患者体内存在特异性和非特异性免疫反应。在本研究中，对20例I型糖尿病患者使用了各种免疫抑制药物和胰岛素，并研究了它们对体外淋巴细胞介导的细胞毒性的影响。20名年龄和性别匹配的健康受试者作为对照。将人胰腺提取物（300微克/毫升蛋白质）包被、用51-铬标记的鸡红细胞用作靶细胞，将分离出的T淋巴细胞用作效应细胞，同时加入或不加入硫唑嘌呤50微克/50微升（威康公司）、环孢素A 5纳克/50微升（山德士公司）和中性胰岛素0.1国际单位/50微升（诺和诺德公司）。细胞毒性程度用细胞毒性能力表示：即最大杀伤靶细胞数。同时评估血清中的胰岛细胞抗体（ICA）和活化T淋巴细胞的数量。在大多数I型糖尿病患者（18/20）中观察到显著的淋巴细胞介导的细胞毒性，而在对照病例中未发现细胞毒性。在所有16例使用硫唑嘌呤或胰岛素的患者中，细胞毒性均降低，与ICA和HLA-DR阳性无关。在所有18例对胰腺提取物具有细胞毒性的患者中，环孢素A使杀伤靶细胞数大幅降低。我们的观察结果表明，环孢素A在体外被证明是最有效的免疫抑制剂。它不仅如先前观察到的那样降低白细胞迁移抑制，还降低淋巴细胞介导的细胞毒性，而后者代表了针对胰腺组织的细胞免疫反应的晚期阶段。
