Liver-derived hepatitis C virus (HCV)-specific CD4(+) T cells recognize multiple HCV epitopes and produce interferon gamma

Virus-specific CD4(+) T-cell response at the site of inflammation is believ ed to play a decisive role for the course of viral disease. In hepatitis C virus (HCV) infection, the majority of studies focused on the peripheral bl ood T-cell response, In this study we analyzed intrahepatic virus-specific CD4(+) T-cell response and compared this with that in the peripheral blood. Liver and blood-derived T-cell lines were studied in 36 patients (18 with chronic hepatitis C and 18 with HCV-associated cirrhosis), Virus-specific i nterferon gamma (IFN-gamma) production at a single cell level to various HC V-proteins (core, nonstnuctural [NS] 3/4, NS5) were determined by enzyme-li nked immunospot (ELIspot), Phenotyping was done by fluorescent-activated ce ll sorter analysis. In approximately half (16 of 36 [44%]) of intrahepatic T-cell lines a significant number of IFN-gamma spots were observed, whereas this was the case in only 19% (7 of 36 T-cell lines) in the blood. In rela tive terms, core and nonstructural proteins were recognized with the same f requency in both compartments, but HCV-specificity was significantly more o ften detected in liver tissue compared with the blood. Hepatitis activity i ndex, viral load, and alanine transaminase levels did not correlate with th e detection of HCV-specific CD4(+) T cells. All T-cell lines were dominated by CD4(+) T cells. In conclusion, HCV-specific CD4(+) T cells are multispe cific, compartmentalize to the liver, and produce IFN-gamma, We speculate t hat our data would support the concept of compartmentalization of specific T cells at the site of inflammation and that a low frequency of specific T cells is associated with failure to clear the virus and a chronic course of disease.