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Expression of MHC class II antigens on islet cells in the pathogenesis of Type I diabetes

I型糖尿病发病机制中胰岛细胞MHC II类抗原的表达

基本信息

批准号：
62480253
负责人：
HANAFUSA Toshiaki
金额：
$ 2.56万
依托单位：
Osaka University
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (B)
财政年份：
1987
资助国家：
日本
起止时间：
1987 至 1988
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-62480253/
关键词：
Type 1 (insulin-dependent) diabetes mellitus Major histocompatibility complex (MHC) class II antigen Pancreatic islet insulitis pathogenesis autoimmunity NODマウス

项目摘要

This study has been performed to clarify the significance of major histocompatibiity complex (MHC) class II antigens on pancreatic beta-cells in the pathogenesis of Type 1 (insulin-dependent) diabetes mellitus.In non-obese diabetic (NOD) mice, an animal model for Type 1 diabetes, I-A antigen, one of mouse MHC class II antigens, was observed in islet cells of all NOD mice examined. Double staining with anti-insulin, glucagon, somatostatin or pancreatic polypeptide antibodies revealed that I-A positive cells corresponded with insulin cells.Following this observation, we examined the pancreas biopsy specimens from 7 newly diagnosed Type 1 diabetic patients. Several features were revealed including marked decrease of insuli-containing cells, preservation of glucagon-containing cells, and various degrees of expression of MHC class I and class II antigens in islet cells and endothelial cells within and around the islets. In one patient, MHC class II antigens were clearly detected in insulin-containing cells. Electron microscopical examination showed the presence of a few lymphocytes infiltrating some islets of another patient.These results suggest that islet cells are destructed through immunological mechanisms and MHC class II antigens on insulin-containing cells may play an important role in the pathogenesis of Type 1 diabetes.

本研究旨在阐明主要组织相容性复合体（MHC） II类抗原对胰腺β细胞在1型（胰岛素依赖性）糖尿病发病机制中的意义。在非肥胖型糖尿病（NOD）小鼠中，作为1型糖尿病的动物模型，在所有NOD小鼠的胰岛细胞中均可见到小鼠MHC II类抗原之一的I-A抗原。抗胰岛素、胰高血糖素、生长抑素或胰腺多肽抗体双染色显示I-A阳性细胞与胰岛素细胞对应。根据这一观察，我们检查了7例新诊断的1型糖尿病患者的胰腺活检标本。结果显示，含胰岛素细胞明显减少，含胰高血糖素细胞保留，胰岛细胞和胰岛内及周围内皮细胞中不同程度的MHC I类和II类抗原表达。在一名患者中，MHC II类抗原在含胰岛素的细胞中被清楚地检测到。电镜检查显示有少量淋巴细胞浸润另一个病人的胰岛。这些结果表明胰岛细胞通过免疫机制被破坏，含胰岛素细胞上的MHC II类抗原可能在1型糖尿病的发病机制中起重要作用。