AUTOIMMUNE DIABETES CAN BE INDUCED IN TRANSGENIC MAJOR HISTOCOMPATIBILITY COMPLEX CLASS-II-DEFICIENT MICE
AUTOIMMUNE DIABETES CAN BE INDUCED IN TRANSGENIC MAJOR HISTOCOMPATIBILITY COMPLEX CLASS-II-DEFICIENT MICE
复制标题
DOI：
10.1084/jem.178.2.589
复制
发表时间：
1993-08-01
影响因子：
15.3
通讯作者：
GLIMCHER, LH
中科院分区：
文献类型：
--
作者：
LAUFER, TM;VONHERRATH, MG;GLIMCHER, LH
胰岛素依赖型糖尿病(IDDM)是一种自身免疫性疾病，以高血糖和单核细胞浸润的胰岛素分泌的胰岛细胞为特征。人类对IDDM的易感性与II类主要组织相容性复合体(MHC)有关，在疾病过程中，胰岛细胞经常异常地II类阳性。我们使用了两个最近描述的转基因品系来研究II类分子和CD4+T细胞在自身免疫性胰岛素炎发病中的作用。由于Abeta(B)基因的定向破坏而继发的II类缺陷小鼠被培育成携带针对内分泌胰腺的淋巴细胞性脉络膜脑膜炎病毒(LCMV)糖蛋白(GP)转基因的小鼠。我们的结果表明，有或没有GP转基因的II类缺陷动物对整个LCMV都能产生正常的细胞毒性T淋巴细胞反应。在感染LCMV后，GP转基因II类缺陷动物与其II类阳性窝产仔一样迅速发展为高血糖。对GP转基因II类缺陷动物的组织切片的组织学检查显示，胰岛中有淋巴细胞渗透，这与它们的II类阳性仔鼠的区别仅在于没有渗透的CD4+T细胞。这些结果表明，在这种自身免疫性糖尿病模型中，CD4+T细胞和MHC II类分子不是疾病发展所必需的。
Insulin-dependent diabetes mellitus (IDDM) is an autoimmune disease marked by hyperglycemia and mononuclear cell infiltration of insulin-producing beta islet cells. Predisposition to IDDM in humans has been linked to the class II major histocompatibility complex (MHC), and islet cells often become aberrantly class II positive during the course of the disease. We have used two recently described transgenic lines to investigate the role of class II molecules and CD4+ T cells in the onset of autoimmune insulitis. Mice that are class II deficient secondary to a targeted disruption of the Abeta(b) gene were bred to mice carrying a transgene for the lymphocytic choriomenigitis virus (LCMV) glycoprotein (GP) targeted to the endocrine pancreas. Our results indicate that class II-deficient animals with and without the GP transgene produce a normal cytotoxic T lymphocyte response to whole LCMV. After infection with LCMV, GP-transgenic class II-deficient animals develop hyperglycemia as rapidly as their class II-positive littermates. Histologic examination of tissue sections from GP-transgenic class II-deficient animals reveals lymphocytic infiltrates of the pancreatic islets that are distinguishable from those of their class II-positive littermates only by the absence of infiltrating CD4+ T cells. These results suggest that in this model of autoimmune diabetes, CD4+ T cells and MHC class II molecules are not required for the development of disease.