CROSS-LINKING OF FC-GAMMA-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 p articles are frequently observed in circulation. The IC leads to cross -linking of Fc gamma receptors (Fc gamma R) on monocytes and exerts im munoinhibitory function. To test the roles of IC in HCV-specific cytot oxic T lymphocyte (CTL) induction, we generated HCV CTL from periphera l blood mononuclear cells of chronic hepatitis C patients with or with out HCV-IC- or immunoglobulin G (IgG)-coated culture plates and compar ed their lytic activities. HCV-IC or adherent IgG, which induces Fc ga mma R cross-linking, significantly reduced CTL activity. Expression of B7-1 on monocytes decreased on adherent IgG. In addition, tumour necr osis factor-alpha (TNF-alpha) and transforming growth factor-beta 1 (T GF-beta 1) production increased from cells on adherent IgG and their m RNA expression in monocytes was enhanced. Anti-TNF-a antibody during i nduction on adherent IgG inhibited lysis; however, anti-TGF-beta compl etely reversed its inhibitory effect. These results demonstrated that HCV-IC or adherent IgG impaired HCV-CTL induction in vitro. The Fc gam ma R-mediated CTL suppression occurred via decreased expression of mon ocyte B7-1 and/or enhanced production of TGF-beta 1.