Abstract
To determine the relationship between hepatitis B virus (HBV) replication and HLA antigen display at a cellular level, the hepatic expression of HLA antigens and HBV genome (HBV-DNA)/gene products (HBsAg/HBcAg) was studied in 24 patients with chronic HBV infection using simultaneously immunohistochemistry and nonisotopicin situ hybridization. The effect of interferon-α and interferon-γ on hepatocyte HLA antigen expression was also evaluated using primary hepatocyte culture in eight patients with chronic HBV infection. HLA class I antigens were detected on hepatocyte membrane in 23 patients (95.8%). Hepatocytes positive for HBcAg and HBV-DNA (cytoplasmic ± nuclear) were either negative or only faintly positive for HLA class I antigens, while hepatocytes positive for HBsAg showed similar levels of HLA class I antigen expression compared with those hepatocytes with no HBsAg expression. In contrast, hepatocytes adjacent to inflammatory infiltrates, whether positive for HBV-DNA or HBV antigens or not, were always strongly positive for HLA class I antigens. Furthermore, active liver histology (N=12) was associated with a higher overall level of hepatic HLA class I antigen expression as compared with inactive histology (N=12,P=0.003). Both interferon-α and interferon-γ treatmentin vitro enhanced hepatocyte HLA class I antigen expression. These data indicate that expression of HLA class I antigens is not enhanced on the membrane of hepatocytes with HBV replication, and this may be one factor that permits the development of viral persistence.
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Gerber AM, Thung SN: Molecular and cellular pathology of hepatitis B. Lab Invest 52:572–590, 1985
Eddleston ALWF: Immunological aspects of hepatitis B infection.In Viral Hepatitis and Liver Disease. AJ Zuckerman (ed). Alan R. Liss, New York, 1988, pp 603–605
Chisari FV, Ferrari C, Mondelli MU: Hepatitis B virus structure and biology. Microb Pathog 6:311–325, 1989
Lautenschlager I, Taskinen E, Inkinsen K, Lehto VP, Virtanen I, Hayry P: Distribution of the major histocompatibility complex antigens on different cellular components of human liver. Cell Immunol 15:191–200, 1984
Harris H, Gill T: Expression of class I transplantation antigens. Transplantation 42:109–117, 1986
Montano L, Miescher GC, Goodall AH, Wiedmann KH, Janossy G, Thomas HC: Hepatitis B virus and HLA antigen display in the liver during chronic hepatitis B virus infection. Hepatology 2:557–561, 1982
Chu CM, Shyu WC, Kuo RW, Liaw YF: HLA class I antigen display on hepatocyte membrane in chronic hepatitis virus infection: Its role in the pathogenesis of chronic type B hepatitis. Hepatology 7:1311–1316, 1987
Yoshie O, Schmidt H, Reddy ESP, Weissman S, Lengyel P: Mouse interferons enhance the accumulation of a human HLA RNA and protein in transfected mouse and hamster cells. J Biol Chem 257:13169–13172, 1982
Baldwin AS, Sharp PA: Two transcription factors, NF-kB and H2TF1, interact with a single regulatory sequence in the class I major histocompatibility complex promoter. Proc Natl Acad Sci USA 85:723–727, 1988
Franco A, Barnaba V, Natali P, Balsano C, Musca A, Balsano F: Expression of Class I and II major histocompatibility complex antigens on human hepatocytes. Hepatology 8:449–454, 1988
Kato Y, Nakagawa H, Kobayashi K, Hattori N, Hatano K: Interferon production by peripheral lymphocytes in HBsAg positive liver disease. Hepatology 2:789–790 1982
Ikeda T, Lever AML, Thomas HC: Evidence for a deficiency of interferon production in patients with chronic hepatitis B virus infection acquired in adult life. Hepatology 6:962–966, 1986
Jilbert AR, Burrell CJ, Gowans EJ, Hertzog PJ, Linnane AW, Mermion BP: Cellular localization of alpha interferon in hepatitis B virus-infected liver tissue. Hepatology 6:957–961, 1986
Nouri-Aria KT, Arnold JC, Davison F, Portmann BC, Meager A, Morris AG, Eddleston ALWF, Alexander GJM, Williams R: Regulation of interferon alpha gene activation in acute and chronic HBV infection. Hepatology 13:1029–1034, 1991
Senaldi G, Lobo-Yeo A, Mowat AP, Mieli-Vergani G, Vergani D: Class I and class II major histocompatibility complex antigens on hepatocytes: Importance of the method of detection and expression in histologically normal and diseased livers. J Clin Pathol 44:107–114, 1991
Lau JYN, Naoumov NV, Alexander GJM, Williams R: Rapid detection of HBV-DNA in liver tissue by in-situ hybridisation and its combination with immunohistochemistry for simultaneous detection of hepatitis B virus (HBV) antigens. J Clin Pathol 44:905–908, 1991
Fagan EA, Guarner P, Perera SDK, Trowbridge R, Rolando N, Davison F, Williams R: Quantitation of hepatitis B virus DNA in serum using the spot hybridisation technique and scintillation counting. J Virol Methods 12:251–262, 1985
Cordell JL, Falini B, Erber WN, Erber WN, Ghosh AK, Abdulaziz Z, MacDonald S, Pulford KAF, Stein H, Mason DY: Immunoenzymatic labelling of monoclonal antibodies using immune complexes of alkaline phosphatase and monoclonal anti-alkaline phosphatase. J Histochem Cytochem 32:219–228, 1984
Naoumov NV, Portmann BC, Tedder RS, Ferns B, Eddleston ALWF, Alexander GJM, Williams R: Detection of hepatitis B virus antigen in liver tissue. Gastroenterology 99:793–198, 1990
Gough NM, Murray K: Expression of the hepatitis B virus surface, core and e antigen genes by stable rat and mouse cell lines. J Mol Biol 162:43–67, 1982
Naoumov NV, Lau JYN, Daniels HM, Alexander GJM, Williams R: Detection of HBV-DNA using a digoxigeninlabelled probe: A rapid technique without loss of sensitivity. J Hepatol 12:382–385, 1991
Lau JYN, Bain VG, Davies SE, Alexander GJM, Williams R: Export of intracellular hepatitis B virus (HBV) surface antigen in chronic HBV infection is related to viral replication. Hepatology 14:416–421, 1991
Lau JYN, Bain VG, Naoumov NV, Smith HM, Alexander GJM, Williams R: Effect of interferon-gamma on the expression of hepatitis B virus antigen in primary hepatocyte culture. Hepatology 14:975–979, 1991
Fukusato T, Gerber MA, Thung SN, Ferrone S, Schaffner F: Expression of HLA class I antigens on hepatocytes in liver disease. Am J Pathol 123:264–270, 1986
Van den Oord JJ, de Vos R, Desmet VJ:In situ distribution of major histocompatibility complex products and viral antigens in chronic hepatitis B virus infection: Evidence that HBc-containing hepatocytes may express HLA-DR antigens. Hepatology 6:981–989 1986
Zhou DX, Taraboulos A, Ou JH, Yen TSB: Activation of class I major histocompatibility complex gene expression by hepatitis B virus. J Virol 64:4025–4028, 1990
Takehara T, Hayashi N, Katayama K, Fusamoto H, Kamada T: Effect of hepatitis B virus replication on expression of HLA class I of hepatocytes. Hepatology 12:973, 1990 (abstract 543)
Wong GHW, Clark-Lewis I, Harris AW, Schrader JW: Effect of cloned interferon-γ on expression on H-2 and Ia antigens on cell lines of hemopoietic, lymphoid, epithelial, fibroblastic and neuronal origin. Eur J Immunol 14:52–56, 1984
Volpes R, van den Oord JJ, De Vos R, Depla E, De Ley M, Desmet AJ: Expression of interferon-γ receptor in normal and pathological human liver tissue. J Hepatol 12:195–202, 1991
Foster GR, Ackrill AM, Goldin RD, Kerr IM, Thomas HC, Stark GR: Expression of the terminal protein region of hepatitis B virus inhibits cellular responses to interferons α and γ and double strand RNA. Proc Natl Acad Sci USA 88:2888–2892, 1991
Pignatelli M, Waters J, Brown D, Lever A, Iwarson S, Scharff Z, Gerety R, Thomas HC: HLA class I antigens on the hepatocyte membrane during recovery from acute hepatitis B virus infection and during interferon therapy in chronic hepatitis B virus infection. Hepatology 6:349–353, 1986
Nagafuchi Y, Scheuer PJ: Expression of β-microglobulin on hepatocytes in acute and chronic type B hepatitis. Hepatology 6:20–23, 1986
Londei M, Lamb JR, Bottazzo GF, Feldmann M: Epithelial cells expressing aberrant MHC class II determinants can present antigen to cloned human T cells. Nature 312:639–641, 1984
Lechler RI, Norcross MA, Germain RN: Qualitative and quantitative studies of antigen-expressing cell function by using IA-expressing L cells. J Immunol 135:2914–2922, 1985
Tiku ML, Liu S, Weaver CW, Teodorescu M, Skosey JL: Class II histocompatibility antigen-mediated immunologic function of normal articular chrondrocytes. J Immunol 135:2923–2928, 1985
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Lau, J.Y.N., Bird, G.L.A., Naoumov, N.V. et al. Hepatic HLA antigen display in chronic hepatitis B virus infection. Digest Dis Sci 38, 888–895 (1993). https://doi.org/10.1007/BF01295916
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DOI: https://doi.org/10.1007/BF01295916