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 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.
First Department of Medicine, Osaka University Medical School, Yamadaoka, Suita, Japan.
T
T
Kanto
N
N
Hayashi
T
T
Takehara
K
K
Katayama
A
A
Ito
K
K
Mochizuki
N
N
Kuzushita
T
T
Tatsumi
Y
Y
Sasaki
A
A
Kasahara
M
M
Hori
D000328:Adult; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D000936:Antigen-Antibody Complex / Q000276:immunology*; D018122:B7-1 Antigen / Q000276:immunology; D002478:Cells, Cultured; D005260:Female; D006526:Hepatitis C / Q000276:immunology*; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis / Q000276:immunology; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000276:immunology*; D017452:Receptors, IgG / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D016212:Transforming Growth Factor beta / Q000096:biosynthesis / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000276:immunology
D000911:Antibodies, Monoclonal; D000936:Antigen-Antibody Complex; D018122:B7-1 Antigen; D017452:Receptors, IgG; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma