Cross-linking of Fc(gamma)-receptor on monocytes inhibits hepatitis C virus-specific cytotoxic T-lymphocyte induction in vitro

Immunology. 1998 Aug;94(4):461-8. doi: 10.1046/j.1365-2567.1998.00538.x.


In hepatitis C virus (HCV) infection, immune complex (IC)-type virus particles are frequently observed in circulation. The IC leads to cross-linking of Fcgamma receptors (FcgammaR) 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 FcgammaR 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-beta1 (TGF-beta1) production increased from cells on adherent IgG and their mRNA expression in monocytes was enhanced. Anti-TNF-alpha 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 FcgammaR-mediated CTL suppression occurred via decreased expression of monocyte B7-1 and/or enhanced production of TGF-beta1.

MeSH terms

  • Adult
  • Antibodies, Monoclonal / pharmacology
  • Antigen-Antibody Complex / immunology*
  • B7-1 Antigen / immunology
  • Cells, Cultured
  • Female
  • Hepatitis C / immunology*
  • Humans
  • Interferon-gamma / biosynthesis
  • Interferon-gamma / immunology
  • Lymphocyte Activation
  • Male
  • Middle Aged
  • Monocytes / immunology*
  • Receptors, IgG / immunology*
  • T-Lymphocytes, Cytotoxic / immunology*
  • Transforming Growth Factor beta / biosynthesis
  • Transforming Growth Factor beta / immunology
  • Tumor Necrosis Factor-alpha / biosynthesis
  • Tumor Necrosis Factor-alpha / immunology


  • Antibodies, Monoclonal
  • Antigen-Antibody Complex
  • B7-1 Antigen
  • Receptors, IgG
  • Transforming Growth Factor beta
  • Tumor Necrosis Factor-alpha
  • Interferon-gamma