T cell immunity to biliary epithelial antigen in primary biliary cirrhosis.

原发性胆汁性肝硬化中 T 细胞对胆道上皮抗原的免疫。

• 批准号: 04670433
• 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: 1992
• 资助国家: 日本
• 起止时间: 1992 至 1993
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-04670433/
• 关键词: primry biliary cirrhosis; human biliary epithelial antigen; T cell immunity; major histocompatibility antigen complex; 免疫遺伝学; 原発性胆汁性肝硬度; 胆管上皮抗原; HLA‐DNA‐typing

In primary biliary cirrhosis, human biliary antigen p28 can stimulate peripheral blood T lymphocytes. It was also demonstrated that splenic T lymphocytes were cytotoxicic against autologous biliary epithelial cells by microcytotoxicity assay in autopsy patients with primary biliary cirrhosis.DNA typing of HLA class II genes showed that DRBl^<**>0803 is one of HLA class II genes related to the development of the disease. On the other hand, HLA class I.tumor necrosis factor-alpha genes(RFLP of TNF-alpha/ Ncol, 5.5kb) and transportor gene( Tap2/Ringll) are not associated with the disease.Interretingly, T Iymphocytes of DRBl^<**>0803 positive patients more strongly stimulated with p28, in comparison with DRBl^<**>0803 negative patients.In conclusion, p28 may be one of target antigens involved in the pathogenesis of primary biliary cirrhosis. Although inner amino asid sequense of p28 is not determined, analysis of interaction between p28, Tcell receptor and DRBl^<**>0803 is important in understanding the mechanism of biliary duct injury.

在原发性胆汁性肝硬化中，人胆汁抗原p28可刺激外周血T淋巴细胞。对原发性胆汁性肝硬化患者尸检标本进行的微量细胞毒试验表明，脾T淋巴细胞对自体胆管上皮细胞具有细胞毒作用，HLA Ⅱ类基因分型结果表明，DRB 1 ^** 0803是与原发性胆汁性肝硬化发生发展有关的HLA Ⅱ类基因之一。另一方面，HLA I类肿瘤坏死因子-α基因（TNF-α/NcoI的RFLP，5.5kb）和转运蛋白基因有趣的是，与DRB1 ^**> 0803阴性患者相比，DRB1 ^**> 0803阳性患者的T淋巴细胞更强地被p28刺激。p28可能是参与原发性胆汁性肝硬化发病的靶抗原之一。虽然p28的内部氨基酸序列尚未确定，但分析p28、T细胞受体和DRB1~（**）0803之间的相互作用对于理解胆管损伤的机制具有重要意义。

项目成果

大西三朗: "自己免疫性肝炎" 日本医学館, 81 (1992)

大西三郎：“自身免疫性肝炎”日本医学博物馆，81（1992）

S.Onishi: "Cytotoxic activity of spleen-derived T lymphoytes against autologous biliary epithelical cells in autopsy patients with primary biliary" Liver. 13. 188-192 (1993)

S.Onishi：“原发性胆道肝脏尸检患者中脾源性 T 淋巴细胞对自体胆道上皮细胞的细胞毒性活性”。

S.Onishi: "Assessment of LAK activity andgamma-interferon producture in patients with small hepatocellular carcinomas" Hepatology. 17. 781-787 (1993)

S.Onishi：“小肝细胞癌患者 LAK 活性和γ-干扰素产物的评估”肝病学。

大西三朗: "1993 今日の治療指針" 医学書院, (1993)

大西三郎：“1993 年今天的治疗指南”Igakushoin，（1993）

Hiromi Himeno: "Administration of 1L-2 induces MHC classII expression on the biliary epithelial cello,possibly Hrrough endogenous interferon-γ production." Hepatology. 16. 409-417 (1992)

Hiromi Himeno：“施用 1L-2 会诱导胆管上皮细胞上的 MHC II 类表达，可能是通过内源性干扰素-γ 产生。” 16. 409-417 (1992)。