Differential expression and regulation of MHC products in the endocrine and exocrine cells of the human pancreas.
Differential expression and regulation of MHC products in the endocrine and exocrine cells of the human pancreas.
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人胰腺内分泌和外分泌细胞中 MHC 产物的差异表达和调节。
DOI：
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发表时间：
1986
影响因子：
4.6
通讯作者：
G. Bottazzo
中科院分区：
文献类型：
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作者：
R. Pujol;I. Todd;M. Doshi;D. Gray;M. Feldmann;G. Bottazzo
在包括I型（胰岛素依赖型）糖尿病在内的大多数自身免疫性疾病的靶细胞中已经检测到HLA II类（D/DR）分子的不适当表达。这种现象是由于淋巴细胞或其某些产物的作用的可能性已经通过分析β细胞中HLA产物的体外调节进行了研究。来自25个人胰腺的单层培养物补充了α-干扰素（IFN）、β-干扰素或γ-干扰素、白细胞介素2（IL-2）和活化淋巴细胞的上清液。此外，凝集素和其他各种激素，生物制品和化学品进行了测试。主要组织相容性复合体（MHC）的表达进行了评估，通过双重免疫荧光技术，使用单克隆抗体的非多态性决定簇的I类和II类分子和胰岛激素和其他细胞质抗原的抗体，确定胰腺细胞。γ-IFN和凝集素可平行增强胰岛、外分泌/导管细胞和成纤维细胞中HLA-A、B、C的表达。HLA-D/DR在所有胰腺细胞类型中是可诱导的，除了内分泌胰岛细胞，其不响应于任何刺激（包括来自活化淋巴细胞的上清液）产生II类分子。来自慢性胰腺炎患者腺体的外分泌/导管细胞自发表达II类产物，但胰岛细胞缺乏任何可检测的D/DR。这些数据与最近的观察结果一致，这些观察结果表明，在“糖尿病”胰腺中，β细胞中不适当的II类表达与浸润胰岛的淋巴细胞的存在无关，并使得有必要假设其他因子负责人I型糖尿病中β细胞中的II类诱导。
Inappropriate expression of HLA Class II (D/DR) molecules has been detected in the target cells of most autoimmune diseases including Type I (insulin-dependent) diabetes. The possibility that this phenomenon is due to the action of lymphocytes or some of their products has been investigated by analysing in vitro the modulation of HLA products in Beta cells. Monolayer cultures from 25 human pancreatic glands were supplemented with alpha-interferon (IFN), beta-IFN or gamma-IFN, interleukin 2 (IL-2) and supernatants from activated lymphocytes. In addition, lectins and a variety of other hormones, biological products and chemicals were tested. Major histocompatibility complex (MHC) expression was assessed by double immunofluorescence technique using monoclonal antibodies to non-polymorphic determinants of Class I and Class II molecules and the pancreatic cells were identified by antibodies to islet hormones and other cytoplasmic antigens. gamma-IFN and lectins produced a parallel enhancement of HLA-A,B,C expression in islet, exocrine/ductal cells and fibroblasts. HLA-D/DR was inducible in all pancreatic cell types, except endocrine islet cells which did not produce Class II molecules in response to any of the stimuli including supernatants from activated lymphocytes. Exocrine/ductal cells from glands of patients with chronic pancreatitis spontaneously expressed Class II products, but islet cells were devoid of any detectable D/DR. These data are consistent with recent observations which have indicated that in the 'diabetic' pancreas inappropriate Class II expression in the Beta cells occurs independently of the presence of lymphocytes infiltrating the islets, and make it necessary to postulate that other factors are responsible for the Class II induction in Beta cells in human Type I diabetes.