IMMUNOPATHOGENESIS OF TYPE B VIRAL HEPATITIS

诱发脑梗死的发病机制 B型肝炎病毒肝细胞损伤与病毒清除 (HBV)感染仍有待确定。 相当间接 有证据表明，HBV特异性细胞免疫应答在 在这些过程中发挥核心作用。 这一假设的证据是 缺乏，因为测试它的适当模型系统还没有 存在过 如果假设是正确的， 致病相关的HBV编码的靶抗原完全是 未知 评估所需的试剂、系统和专业知识 免疫应答在损伤和清除中的作用现在已经存在， 在我们的实验室里。 因此，这一长期目标 建议是表征人类细胞免疫反应， 已知的HBV编码的抗原，以描绘 可能与病毒清除和肝脏疾病有关的因素。 本研究将着重探讨HBV抗原特异性的特点， 来源于感染部位的T细胞系和克隆， 损伤（肝脏），也来自患者的外周血， 急性或慢性乙型肝炎。 HBV抗原特异性T细胞将 评估表型、精细特异性、HLA限制和 通过检测抗原特异性辅助、抑制和 细胞毒活性和淋巴因子产生。 我们的初步 结果表明，HBV核衣壳特异性T细胞存在于 外周血不能准确地反映发生事件 在肝脏内的损伤和病毒合成部位。 我们， 因此，打算将这些研究扩展到剩余的HBV 在这个提议中编码抗原。 当这些数据可用时， 将有可能确定HBV抗原特异性T细胞 活化、表型和功能在发病机制上与 病毒诱导的损伤和病毒清除。

The pathogenetic mechanisms responsible for the induction of hepatocellular injury and viral clearance in hepatitis B virus (HBV) infection remain to be determined. Considerable indirect evidence suggests that HBV specific cellular immune response plays a central role in these processes. Proof of this hypothesis is lacking because the appropriate model systems to test it have not existed. Furthermore, if the hypothesis is correct, the pathogenetically relevant HBV encoded target antigens are entirely unknown. The reagents, systems and expertise necessary to assess the role of the immune response in injury and clearance now exist in our laboratory. Therefore, the long term objective of this proposal is to characterize the human cellular immune response to the known HBV-encoded antigens in an effort to delineate the factors potentially involved in viral clearance and liver disease. The study will focus on the characteristics of HBV antigen specific T cell lines and clones derived from the site of infection and injury (liver) and also from the peripheral blood of patients with acute or chronic hepatitis-B. HBV antigen-specific T cells will be assessed for phenotype, fine specificity, HLA restriction and function by testing antigen specific helper, suppressor and cytotoxic activities and lymphokine production. Our preliminary results indicate that HBV nucleocapsid specific T cells present in the peripheral blood do not accurately reflect events occurring within the liver at the site of injury and viral synthesis. We, therefore, intend to expand these studies to the remaining HBV encoded antigens in this proposal. When such data is available it will be possible to determine if HBV antigen specific T cell activation, phenotype and function are pathogenetically related to virus induced injury and to viral clearance.