Pujol-Borrell R, Todd I, Doshi M, Bottazzo G F, Sutton R, Gray D, Adolf G R, Feldmann M
Nature. 1987;326(6110):304-6. doi: 10.1038/326304a0.
HLA class II molecules are surface glycoproteins which are essential in the initiation of immune responses. It has been postulated that induction of class II in epithelial cells such as endocrine cells, which are normally class II negative, may result in autoimmunity. In type I diabetes, islet beta cells, the target of the autoimmune process, selectively express class II antigens. But in contrast to most other cell types, islet beta cells are not stimulated to express class II by interferon-gamma (IFN-gamma) and thus the conditions under which this induction occurs have been particularly elusive. The cytotoxins tumour necrosis factor (TNF) and lymphotoxin (LT) synergize with IFN-gamma in a number of activities. We report here that IFN-gamma in combination with either TNF or LT induces islet cell class II expression. This finding has important implications for the pathogenesis of type I diabetes and the understanding of the differential control of class II expression.
人类白细胞抗原（HLA）II类分子是表面糖蛋白，在免疫反应的启动中至关重要。据推测，在内分泌细胞等通常II类阴性的上皮细胞中诱导II类分子表达，可能会导致自身免疫。在I型糖尿病中，作为自身免疫过程靶点的胰岛β细胞选择性表达II类抗原。但与大多数其他细胞类型不同，胰岛β细胞不会被γ干扰素（IFN-γ）刺激而表达II类分子，因此这种诱导发生的条件一直特别难以捉摸。细胞毒素肿瘤坏死因子（TNF）和淋巴毒素（LT）在许多活动中与IFN-γ协同作用。我们在此报告，IFN-γ与TNF或LT联合使用可诱导胰岛细胞II类分子表达。这一发现对I型糖尿病的发病机制以及对II类分子表达差异控制的理解具有重要意义。
