IMMUNOBIOLOGY AND PATHOGENESIS OF HEPATOCELLULAR INJURY IN HEPATITIS-B VIRUS TRANSGENIC MICE

IMMUNOBIOLOGY AND PATHOGENESIS OF HEPATOCELLULAR INJURY IN HEPATITIS-B VIRUS TRANSGENIC MICE
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DOI:
10.1126/science.1691527
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发表时间:
1990-04-20
期刊:
影响因子:
56.9
通讯作者:
CHISARI, FV
CHISARI, FV
中科院分区:
综合性期刊1区
文献类型:
--
作者:
MORIYAMA, T;GUILHOT, S;CHISARI, FV

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由于缺乏合适的实验模型,对B型肝炎病毒(HBV)编码抗原的免疫应答在肝细胞损伤发病机制中的作用尚未确定。HBV包膜转基因小鼠用于显示HBV编码的抗原在肝细胞表面以主要组织相容性复合物(MHC)I类限制性CD8+细胞毒性T淋巴细胞可识别的形式表达,所述细胞毒性T淋巴细胞对主要包膜多肽内的显性T细胞表位具有特异性,并且所述细胞毒性T淋巴细胞可识别HBV特异性抗体。这两种相互作用导致体内肝细胞死亡,提供了直接证据表明,人HBV感染中的肝细胞损伤也可能是免疫介导的。
The role of the immune response to hepatitis B virus (HBV)-encoded antigens in the pathogenesis of liver cell injury has not been defined because of the absence of appropriate experimental models. HBV envelope transgenic mice were used to show that HBV-encoded antigens are expressed at the hepatocyte surface in a form recognizable by major histocompatibility complex (MHC) class I-restricted, CD8+ cytotoxic T lymphocytes specific for a dominant T cell epitope within the major envelope polypeptide and by envelope-specific antibodies. Both interactions led to the death of the hepatocyte in vivo, providing direct evidence that hepatocellular injury in human HBV infection may also be immunologically mediated.