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

本项目的目的是在体外研究乙肝病毒感染过程中抗原特异性T细胞免疫反应和细胞毒作用。检测来自外周血的单个核细胞对重组乙肝病毒相关抗原的增殖反应。(1)急性肝炎(AH)、慢性肝炎(CH)和HBeAg阳性无症状携带者(ASC)对r-HBs Ag、preS2 SAG和preS1 preS2 SAg的反应均呈低水平，而在抗HBe阳性的ASC中则略高。(2)急性肝炎急性期T细胞对r-HBcAg有较强的增殖反应，恢复期T细胞对r-HBcAg反应减弱。(3)在慢性肝炎中，除少数血清中有IgM抗-HBc阳性或急性加重前HBeAg阳性者外，其余患者对r-HBcAg的应答均较低。(4)急性肝炎恢复期患者肝脏来源的单个核细胞对r-HBcAg无反应。这些结果提示，T细胞对HBcAg的敏感性与肝细胞的损伤是一致的，T细胞对HBV抗原的反应不足可能是导致乙肝病毒感染持续存在的重要原因。根据这些结果，我们试图从AH患者中获得HBcAg特异性T细胞克隆。虽然我们建立了几个针对HBcAg的T细胞系，但由于克隆过程中对抗原的增殖能力较差，T细胞克隆一直未获成功。

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.