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Autoimmunity to Bile Duct Epithelial Cells in Patients with Primary Billary Cirrhosis

原发性胆汁性肝硬化患者胆管上皮细胞的自身免疫

基本信息

批准号：
62570329
负责人：
ONISHI Saburo
金额：
$ 1.02万
依托单位：
Kochi Medical School
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
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

项目摘要

Primary biliary cirrhosis (PBC) is an enigmatic chronic liver disease characterized by progressive and inflammatory obliteration of intrahepatic bile ducts where autoimmune-mediated pathogenesis is considered to be responsible for damages to the target tissue. We reported a predominant role of T cell mediated immunity in the pathogenesis of PBC, because peripheral lymphocytes were sensitized to partially purified biliary antigen in leukocyte migration inhibition test, while antibody to the same antigen was not detected in the sera of PBC patients.In this study, histoimmunochemical investigation showed that OKT8 positive and Leul5 negative T cell population, phenotypically cytotoxic T cells infiltrated into damaged bile ducts in PBC. Furthermore, splenic T lymphocytes but not non-T lymphocytes were shown to be cytotoxic against autologous biliary epithelial( BE ) cells at effector to target ratios of 100 and 200 in 10hrs'^<51>Cr% release. BE cells were obtained from autopsy specimen by … More pumping PBS solution supplemented with EDTA, DNAase and Disparse into bile ducts. Specificity of cytotoxicity was shown by cold target inhibition using autologous BE cells. A phenotype of effectors was shown to be CD8 positive by negative selection using complement lysis with OKT8 or OKT4 monoclonal antibody. Next, biliary epithelial antigens were identified by SDS-PAGE and Western blotting of partially purified biliary antigen in which rabbit anti-biliary antigen specific to human biliary epithelial cells was used to detect the antigens. B1, B2 and B3 antigens with more than 200 KD mw were detected. They were eluted electophoretically from gels separately and used as antigens to stimulate T cell proliferation. Blastgensis to B1 at a constriction of 1.0 to 0.1 mc g/ml was detected exclusively in PBC but not in other liver diseases while blastgenesis to B3 was not detected in PBC.These data strongly point to the role of T cell immunity against biliary epithelial antigen; B1 antigen in the pathogenesis of PBC. Less

原发性胆汁性肝硬化（PBC）是一种以肝内胆管进行性炎症性闭塞为特征的慢性肝病，其自身免疫介导的发病机制被认为是导致靶组织损伤的原因。我们报道了T细胞介导的免疫在PBC发病中的主导作用，因为外周血淋巴细胞在白细胞移动抑制试验中对部分纯化的胆汁抗原敏感，而PBC患者血清中未检测到针对相同抗原的抗体。PBC中表型细胞毒性T细胞浸润到受损的胆管中。此外，脾T淋巴细胞而非非T淋巴细胞显示出在10小时的μ Cr%释放中在100和200的效应与靶比下对自体胆管上皮（BE）细胞具有细胞毒性<51>。BE细胞从尸检标本中获得， ...更多信息将补充有EDTA、DNAase和Disparse的PBS溶液泵入胆管。使用自体BE细胞通过冷靶抑制显示细胞毒性的特异性。通过使用OKT 8或OKT 4单克隆抗体进行补体裂解的阴性选择，显示效应子的表型为CD 8阳性。接着，通过部分纯化的胆汁抗原的SDS-PAGE和Western印迹鉴定胆汁上皮抗原，其中使用对人胆汁上皮细胞特异性的兔抗胆汁抗原来检测抗原。检测到分子量大于200 KD的B1、B2和B3抗原。它们分别从凝胶电泳洗脱并用作刺激T细胞增殖的抗原。在1.0 ~ 0.1mcg/ml的收缩中，PBC仅检测到B_1的胚细胞生成，而在其他肝病中未检测到B_3的胚细胞生成。这些数据有力地指出了T细胞对胆管上皮抗原、B_1抗原的免疫在PBC发病中的作用。少