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Analysis of Mechanism of Hepatocyte Injury Byautigcn-Specific Celular Immcne Nespouses During Hepatitis B Virus (HBV) Infection

乙型肝炎病毒(HBV)感染期间特异性细胞免疫性肝细胞损伤机制分析

基本信息

批准号：
63570326
负责人：
YAMADA Gotaro
金额：
$ 1.28万
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：
1988
资助国家：
日本
起止时间：
1988 至 1990
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-63570326/
关键词：
Hipatitis B Cellular immunity Hepatoeyte injury ウィルス抗原特異的T細胞

项目摘要

This project aim to demonstrate antigen-specific T cell immune response and cytotoxicity during HBV infection in vitro. Proliferative responses of mononuclear cells derived from peripheral blood to recombinant HBV-related antigens are examined. (1) The responses to r-HBsAg, preS2+SAg and preS1+preS2+SAg showed low levels in patients with Acute Hepatitis (AH), Chronic Hepatitis (CH) and HBeAg-positive Asymptomatic Carrier (ASC), while they were slightly higher in anti-HBe positive ASC. (2) Strong T cell proliferation to r-HBcAg was noted in most of patients with AH during acute phase of illness and become decreased in the recovery phase. (3) In CH, the response to r-HBcAg remained low except several HBeAg-positive cases who had IgM anti-HBc in sera or were before acute exacerbation. (4) Mononuclear cells derives from liver of patients from AH with recovery phase didn't respond to r-HBcAg. These results suggest that T cell sensitization to HBcAg occur coincide with liver cell injury and inadequate T cell responses to HBV antigens may be more important in the persistance of HBV infection. From these results, we these results, we tried to make HBcAg-specific T cell clones from patients with AH. Although we made several T cell lines to HBcAg, T cell clones have been unsuccessful for poor poliferation to antigen during cloning process.

本项目旨在体外研究HBV感染过程中抗原特异性T细胞免疫应答和细胞毒性。检测外周血单个核细胞对重组HBV相关抗原的应答。(1)急性肝炎（AH）、慢性肝炎（CH）和HBeAg阳性无症状携带者（ASC）对r-HBsAg、preS2 + SAg和preS1 + preS2 + SAg的应答水平较低，而抗-HBe阳性ASC则略高。(2)大部分AH患者急性期T细胞对r-HBcAg的增殖反应较强，恢复期T细胞增殖反应减弱。(3)在CH中，除了几个HBeAg阳性的病例血清中有IgM抗-HBc或在急性加重之前，对r-HBcAg的反应仍然很低。(4)AH恢复期患者肝源性单核细胞对r-HBcAg无反应。这些结果表明，T细胞对HBcAg的敏感性与肝细胞损伤同时发生，并且T细胞对HBV抗原的应答不足可能在HBV感染的持续性中更重要。根据这些结果，我们试图从AH患者中制备HBcAg特异性T细胞克隆。虽然我们已经建立了几种针对HBcAg的T细胞系，但由于克隆过程中对抗原的增殖能力差，T细胞克隆一直不成功。