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Liver‐Derived Hepatitis C Virus (HCV)‐Specific CD4 + T Cells Recognize Multiple HCV Epitopes and Produce Interferon Gamma
Author(s) -
Schirren Carl Albrecht,
Jung MariaChristina,
Gerlach Joern Tilman,
Worzfeld Thomas,
Baretton Gustavo,
Mamin Maxim,
Hubert Gruener Norbert,
Houghton Michael,
Pape Gerd Rudolf
Publication year - 2000
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1053/jhep.2000.9635
Subject(s) - elispot , hepatitis c virus , hepatitis c , interferon , immunology , virology , t cell , biology , hepacivirus , virus , medicine , immune system
Virus‐specific CD4 + T‐cell response at the site of inflammation is believed 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 blood 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 interferon gamma (IFN‐γ) production at a single cell level to various HCV‐proteins (core, nonstructural [NS] 3/4, NS5) were determined by enzyme‐linked immunospot (ELIspot). Phenotyping was done by fluorescent‐activated cell sorter analysis. In approximately half (16 of 36 [44%]) of intrahepatic T‐cell lines a significant number of IFN‐γ spots were observed, whereas this was the case in only 19% (7 of 36 T‐cell lines) in the blood. In relative terms, core and nonstructural proteins were recognized with the same frequency in both compartments, but HCV‐specificity was significantly more often detected in liver tissue compared with the blood. Hepatitis activity index, viral load, and alanine transaminase levels did not correlate with the 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 multispecific, compartmentalize to the liver, and produce IFN‐γ. We speculate that 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.