Monocyte-dependent cell death of T lymphocyte subsets in chronic hepatitis C.
A high incidence of viral persistence and progression to chronic hepatitis are characteristic features of hepatitis C virus (HCV) infection. Since T lymphocytes play a critical role in virus clearance, their abnormalities in undergoing apoptosis may cause the insufficient antiviral immune responses leading to persistent viral infection. Recent reports have suggested that monocyte-dependent cell death (MDCD) is a mechanism of T lymphocyte apoptosis in chronic viral infection. The current study was designed to monitor apoptosis of CD4+ and CD8+ T lymphocyte subsets in co-culture with CD14+ monocytes under the apoptotic stimuli in patients with chronic hepatitis C. Cell mortalities of CD4+ and CD8+ T lymphocyte subsets from patients exhibiting various degrees of chronic hepatitis C were increased to a greater extent when incubated with CD14+ monocyte subset in medium containing phorbol 12-myristate 13-acetate. The current observations demonstrate that MDCD of CD4+ and CD8+ T lymphocyte subsets may provide a cellular basis for immune dysfunction which results in insufficient viral clearance and progression of liver disease in chronic HCV infection.
Nakamoto
Y
Y
First Department of Internal Medicine, Faculty of Medicine, Kanazawa University, 13-1 Takara-machi, Kanazawa, 920-8641, Kanazawa, Japan.
Kaneko
S
S
Kobayashi
K
K
D017209:Apoptosis / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000473:pathology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000473:pathology; D016923:Cell Death / Q000276:immunology; D002478:Cells, Cultured; D018920:Coculture Techniques; D053222:Fas Ligand Protein; D019698:Hepatitis C, Chronic / Q000276:immunology* / Q000473:pathology*; D006801:Humans; D008024:Ligands; D018950:Lipopolysaccharide Receptors / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology; D008562:Membrane Glycoproteins / Q000502:physiology; D009000:Monocytes / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000473:pathology*; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology; D019014:fas Receptor / Q000378:metabolism
C505661:FASLG protein, human; D053222:Fas Ligand Protein; D008024:Ligands; D018950:Lipopolysaccharide Receptors; D008562:Membrane Glycoproteins; D014409:Tumor Necrosis Factor-alpha; D019014:fas Receptor