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. (C) 2001 Elsevier Science B.V. All rights reserved.