干扰素-γ对胰腺β细胞的作用导致I类主要组织相容性复合体上调，但不会引发糖尿病。
IFN-gamma action on pancreatic beta cells causes class I MHC upregulation but not diabetes.
作者信息
Thomas H E, Parker J L, Schreiber R D, Kay T W
机构信息
Autoimmunity and Transplantation Division, Walter and Eliza Hall Institute of Medical Research, Victoria 3050, Australia.
出版信息
J Clin Invest. 1998 Sep 15;102(6):1249-57. doi: 10.1172/JCI2899.
Abstract
We have generated transgenic nonobese diabetic (NOD) mice expressing dominant negative mutant IFN-gamma receptors on pancreatic beta cells to investigate whether the direct effects of IFN-gamma on beta cells contribute to autoimmune diabetes. We have also quantitated by flow cytometry the rise in class I MHC on beta cells of NOD mice with increasing age and degree of islet inflammatory infiltrate. Class I MHC expression increases gradually with age in wild-type NOD mice; however, no such increase is observed in the transgenic beta cells. The transgenic mice develop diabetes at a similar rate to that of wild-type animals. This study dissociates class I MHC upregulation from progression to diabetes, shows that the rise in class I MHC is due to local IFN-gamma action, and eliminates beta cells as the targets of IFN-gamma in autoimmune diabetes.
摘要
我们构建了在胰腺β细胞上表达显性负性突变干扰素-γ受体的转基因非肥胖糖尿病（NOD）小鼠，以研究干扰素-γ对β细胞的直接作用是否会导致自身免疫性糖尿病。我们还通过流式细胞术对随着年龄增长和胰岛炎性浸润程度增加的NOD小鼠β细胞上I类主要组织相容性复合体（MHC）的增加进行了定量分析。在野生型NOD小鼠中，I类MHC表达随年龄逐渐增加；然而，在转基因β细胞中未观察到这种增加。转基因小鼠患糖尿病的速率与野生型动物相似。这项研究将I类MHC上调与糖尿病进展分离开来，表明I类MHC的增加是由于局部干扰素-γ作用，并排除了β细胞作为自身免疫性糖尿病中干扰素-γ的靶标。
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Interferon-gamma impacts at multiple points during the progression of autoimmune diabetes.干扰素-γ在自身免疫性糖尿病进展过程中的多个环节发挥作用。
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