Immunobiology and pathogenesis of hepatocellular injury in hepatitis B virus transgenic mice

• Published in: Science (American Association for the Advancement of Science) Vol. 248; no. 4953; pp. 361 - 364
• Main Authors: MORIYAMA, T, GUILHOT, S, KLOPCHIN, K, MOSS, B, PINKERT, C. A, PALMITER, R. D, BRINSTER, R. L, KANAGAWA, O, CHISARI, F. V
• Format: Journal Article
• Language: English
• Published: Washington, DC American Association for the Advancement of Science 20.04.1990; The American Association for the Advancement of Science
• Subjects: Abnormalities; Amino Acid Sequence; Animals; Biological and medical sciences; Cell Line, Transformed; Cytotoxicity, Immunologic; Development and progression; Disease; Epitopes - immunology; Fundamental and applied biological sciences. Psychology; Genetically modified mice; Hepatitis; Hepatitis B; Hepatitis B - immunology; Hepatitis B Surface Antigens - genetics; Hepatitis B Surface Antigens - immunology; Hepatocytes; Histocompatibility Antigens Class I - immunology; Liver - immunology; Liver cells; Medical research; Mice; Mice, Transgenic; Microbiology; Molecular Sequence Data; Physiological aspects; Replicative cycle, interference, host-virus relations, pathogenicity, miscellaneous strains; Simian virus 40; T-Lymphocytes, Cytotoxic - immunology; T-Lymphocytes, Regulatory - immunology; Transfection; Virology; Viruses; Hepatitis B surface antigen; Pathogenesis; Cytotoxicity test; Rodentia; Transgenic animal; Mechanism; Infection; Virus; Vertebrata; Viral hepatitis; Mammalia; Hepatocyte; Mouse; Hepadnaviridae; Viral disease; Infiltration; Coat protein; Hepatitis B virus; Virus envelope; Lymphocyte
• ISSN: 0036-8075; 1095-9203
• DOI: 10.1126/science.1691527

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.