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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
Author(s) -
van den Oord Joost J.,
De Vos Rita,
Desmet Valeer J.
Publication year - 1986
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1002/hep.1840060529
Subject(s) - hbcag , antigen , cytotoxic t cell , biology , major histocompatibility complex , pan t antigens , immunology , human leukocyte antigen , virology , histocompatibility , immunoelectron microscopy , hbsag , hepatitis b virus , virus , immunohistochemistry , antibody , monoclonal antibody , biochemistry , in vitro
Using a double‐staining immunohistochemical procedure, the topographical relationship between viral antigens on the one hand and the expression of major histocompatibility complex products by hepatocytes on the other hand was analyzed in a series of 19 liver biopsies from patients with chronic hepatitis B virus infection. In areas of piecemeal necrosis, periportal hepatocytes demonstrated Class I major histocompatibility complex products or HLA‐A, B and C antigens, but did not show a preferential expression of either HBcAg or HBsAg. The cellular infiltrate of piecemeal necrosis consisted of helper/inducer and suppressor/cytotoxic T‐lymphocytes, and was admixed in four cases with branching dendritic processes of sinusoidal lining cells which strongly expressed Class II major histocompatibility complex products or HLA‐DR antigens. The latter surrounded small groups of periportal hepatocytes. In areas of spotty necrosis, the hepatocytes expressed HLA‐A, B and C antigens in all cases, and were admixed with variable numbers of suppressor/cytotoxic T‐lymphocytes. In 14 cases, the clustered hepatocytes in areas of spotty necrosis expressed HLA‐DR antigens, associated in 11 of the cases with immunoreactive HBcAg in the nuclei of some of the HLA‐DR‐positive hepatocytes. Immunoelectron microscopy, performed in one such case, demonstrated the presence of HLA‐DR antigen in a discontinuous pattern at the plasma membrane of some hepatocytes, together with the presence of core particles in the nucleus of HLA‐DR‐positive hepatocytes. Our findings further contribute to the growing evidence that HBcAg represents the major target antigen for T‐cell attack in areas of spotty necrosis. It is suggested that lymphokines, e.g., γ‐intereron, secreted by nearby lymphocytes represent the eliciting agent for HLA‐DR production and expression by hepatocytes in areas of spotty necrosis in chronic hepatitis B virus infection.