title: Low frequency of cytotoxic liver-infiltrating T lymphocytes specific for endogenous processed surface and core proteins in chronic hepatitis B.
abstract: To investigate the role of hepatitis B virus (HBV)-specific CD8+ T cells in chronic hepatitis B, the lytic activity of peripheral blood mononuclear cells (PBMC) and liver-infiltrating T cell clones and cytotoxic T cell (CTL) lines stimulated by recombinant vaccinia virus-infected cells were analyzed. Autologous and allogeneic Epstein-Barr virus-transformed B cells infected with vaccinia vectors (VAC) that contain sequences of the surface (S), secretory core (E), cytoplasmatic core (C) VAC antigen of HBV, or the wild-type (WT) VAC served as target cells. ELISA and immunoblotting showed HBV antigen expression in infected cells. Neither PBMC nor C- or E-VAC-stimulated CTL lines showed specific lytic activity. However, S-VAC stimulated blood- and liver-derived CTL from 2 patients with hepatitis B lysed autologous S-VAC but not WT-VAC-infected target cells. One of 158 CD8+ T cell clones from 6 patients with active hepatitis B lysed autologous, but not allogeneic, S-VAC-infected targets. Thus, CTL are present among liver-infiltrating T cells in chronic hepatitis B that recognize endogenously processed hepatitis B surface antigen but not HBc or HBe antigen. The lack of core-specific CTL may contribute to failure in virus elimination in chronic inflammation.
authors.affiliation: Department of Internal Medicine, University of Mainz, Germany.
authors.forename: H F
authors.initials: HF
authors.lastname: Löhr
authors.forename: G
authors.initials: G
authors.lastname: Gerken
authors.forename: H J
authors.initials: HJ
authors.lastname: Schlicht
authors.forename: K H
authors.initials: KH
authors.lastname: Meryer zum Büschenfelde
authors.forename: B
authors.initials: B
authors.lastname: Fleischer
mesh_terms: D001402:B-Lymphocytes; D002465:Cell Movement; D002472:Cell Transformation, Viral; D003602:Cytotoxicity, Immunologic; D005805:Genes, MHC Class I / Q000276:immunology; D006509:Hepatitis B / Q000276:immunology*; D006511:Hepatitis B Antigens / Q000235:genetics / Q000276:immunology*; D006512:Hepatitis B Core Antigens / Q000235:genetics / Q000276:immunology; D006514:Hepatitis B Surface Antigens / Q000235:genetics / Q000276:immunology; D006513:Hepatitis B e Antigens / Q000276:immunology; D006521:Hepatitis, Chronic / Q000276:immunology*; D004854:Herpesvirus 4, Human; D006801:Humans; D008099:Liver / Q000276:immunology*; D011499:Protein Processing, Post-Translational; D011994:Recombinant Proteins / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014616:Vaccinia virus / Q000235:genetics
chemical_list: D006511:Hepatitis B Antigens; D006512:Hepatitis B Core Antigens; D006514:Hepatitis B Surface Antigens; D006513:Hepatitis B e Antigens; D011994:Recombinant Proteins