Cross-linking of Fcγ-receptor on monocytes inhibits hepatitis C virus-specific cytotoxic T-lymphocyte induction in vitro

In hepatitis C virus (HCV) infection, immune complex (IC)-type virus particles are frequently observed in circulation. The IC leads to cross-linking of Fc gamma receptors (Fc gamma R) on monocytes and exerts immunoinhibitory function. To test the roles of IC in HCV-specific cytotoxic T lymphocyte (CTL) induction, we generated HCV CTL from peripheral blood mononuclear cells of chronic hepatitis C patients with or without HCV-IC- or immunoglobulin G (IgG)-coated culture plates and compared their lytic activities. HCV-IC or adherent IgG, which induces Fc gamma R cross-linking, significantly reduced CTL activity. Expression of B7-1 on monocytes decreased on adherent IgG. In addition, tumour necrosis factor-alpha (TNF-alpha) and transforming growth factor-beta 1 (TGF-beta 1) production increased from cells on adherent IgG and their mRNA expression in monocytes was enhanced. Anti-TNF-a antibody during induction on adherent IgG inhibited lysis; however, anti-TGF-beta completely reversed its inhibitory effect. These results demonstrated that HCV-IC or adherent IgG impaired HCV-CTL induction in vitro. The Fc gamma R-mediated CTL suppression occurred via decreased expression of monocyte B7-1 and/or enhanced production of TGF-beta 1.