Immunopathological Study for Pathogenesis of Chronic Hepatitis, Type C

慢性丙型肝炎发病机制的免疫病理学研究

• 批准号: 04670432
• 负责人: YAMADA Gotaro
• 金额: $ 1.34万
• 依托单位: Okayama University
• 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 1994
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-04670432/
• 关键词: Chronic hepatitis, C; Mechanism of liver injury; T cell cytotoxicity; HLA antigens; Adhesion molecules; In situ hybridization; HCV core antigen; HCV-RNA; HCV抗原; HLA core抗原; HLA core抗原、; 免疫組織化学; Insitu hybridization

In order to clarify the mechanism of liver injuries in chronic hepatitis, type C,we investigated immunopathological findings of hepatitis C virus (HCV) and cellular immune responses in liver biopsy specimens. An immunohistochemical method using anti-HCV core antigen (anti-HCc : anti-CP-9) and in situ hybridization technique using T-T dimerized oligo cDNA probes were applied. Cellular immune responses in liver tissues were observed by indirect immunoperoxidase method using anti-CD8, anti-CDllb, anti-CD4, anti-CD22 and anti-CD57 for the subpopulation of lymphocytes and T cell subsets. Anti-ABC,anti-DR,anti-DP,and anti-DQ were studies for HLA antigens. Anti-ICAM-1, anti-VCAM-1 and anti-LFA-1 were used for detection of adhesion molecules. Expression of FasAg on hepatocytes was also studied by immunoperoxidase method usingmouse monoclonal antibodies secreted by B cell hybridomas (clone ZB4 and UB2).In most patients, liver cells with HCcAg and /or HCV-RNA were present in small mumbers and sporadically, but lobular distribution of HCV-positive hepatocytes was observed in some patients. Numerous Tlymphocytes were present immunohistochemically in the liver of patients with chronic active hepatitis, and particularly, numerous OKT8 (+), llb (-1) and LFA-1 (+) CTL infiltrated in areas of piecemeal necrosis and focal necrosis. On surface of hepatocytes in these areas, HLA-class 1 and ICAM-1 antigens were membranously expressed. FasAg was also observed diffusely on hepatocytes throughout lobules in most patients with chronic active hepatitis. These findings suggest liver cell injuries in chronic hepatitis C,may be caused by CD8+CTL recognizing HCV and HLA-class 1.

为了阐明慢性丙型肝炎的肝损伤机制，我们研究了肝活检标本中丙型肝炎病毒（HCV）的免疫病理结果和细胞免疫反应。采用抗hcv核心抗原（抗hcc：抗cp -9）的免疫组织化学方法和T-T二聚寡核苷酸探针原位杂交技术。采用间接免疫过氧化物酶法观察肝组织淋巴细胞亚群和T细胞亚群的抗cd8、抗cdllb、抗cd4、抗cd22和抗cd57的细胞免疫应答。Anti-ABC、anti-DR、anti-DP、anti-DQ进行HLA抗原的检测。采用Anti-ICAM-1、anti-VCAM-1、anti-LFA-1检测粘附分子。利用B细胞杂交瘤（克隆ZB4和UB2）分泌的小鼠单克隆抗体，免疫过氧化物酶法研究了FasAg在肝细胞上的表达。在大多数患者中，携带HCcAg和/或HCV-RNA的肝细胞以少量和零星的形式存在，但在一些患者中观察到hcv阳性肝细胞的小叶分布。慢性活动性肝炎患者肝脏免疫组化可见大量t淋巴细胞，特别是在局部坏死和局灶性坏死区域可见大量OKT8（+）、llb（-1）和LFA-1 (+) CTL浸润。在这些区域的肝细胞表面，hla -1和ICAM-1抗原呈膜性表达。在大多数慢性活动性肝炎患者中，也观察到FasAg弥漫性分布在肝细胞的小叶上。这些发现提示慢性丙型肝炎的肝细胞损伤可能是由CD8+CTL识别HCV和hla - 1类引起的。

项目成果

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山田G

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