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 Bvirus (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 cytoxic 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 ofHBV, 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 bloodand liver-derived CTL from 2 patients with hepatitis B lysed autologous S-VAC but not WTVAC- 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.