title: Features of the CD4+ T-cell response in liver and peripheral blood of hepatitis C virus-infected patients with persistently normal and abnormal alanine aminotransferase levels.
abstract: OBJECTIVE
  The liver is the primary site of hepatitis C virus (HCV) replication; intrahepatic T-cell responses may influence liver disease severity.
  
  
  METHODS
  HCV-specific CD4(+) T-cell reactivity was investigated ex vivo in paired liver tissue and peripheral blood from 42 chronic HCV patients.
  
  
  RESULTS
  The frequencies with which HCV-specific HLA class-II-restricted CD4(+) T-cell proliferation were observed were 29% in liver and 36% in peripheral blood. Among responses, non-structural-3 protein (NS3)-specific T-cell proliferation was dominant but non-exclusive and did rarely occur concurrently in liver infiltrate and peripheral blood suggesting liver compartmentalization of a CD4(+) T-cells population. Compared with 24 patients with abnormal ALT levels, 18 HCV carriers with persistently normal ALT levels had similar serum and liver viral loads but showed: (i) a low-activity grade and stage chronic hepatitis (P<0.001); (ii) less intrahepatic CD4(+) T-lymphocytes (P<0.01); (iii) less frequent intrahepatic (17 vs. 33%) and peripheral (17 vs. 38%) NS3-specific CD4(+) T-cell proliferation; (iv) less often in vitro T-helper (Th)1 (interferon-gamma) cytokine production (2 vs. 18%; P<0.001).
  
  
  CONCLUSIONS
  Our data show a low frequency of intrahepatic HCV-specific HLA class-II-restricted CD4(+) Th1 responses in patients with chronic HCV. However, these Th1 responses are detected more often in those patients with overt clinical and histological disease.
authors.affiliation: Institute of Hepatology, Hospital Pardo de Aravaca, Madrid, Spain.
authors.forename: Miguel A
authors.initials: MA
authors.lastname: Rico
authors.forename: Juan A
authors.initials: JA
authors.lastname: Quiroga
authors.forename: Dolores
authors.initials: D
authors.lastname: Subirá
authors.forename: Esteban
authors.initials: E
authors.lastname: Garcia
authors.forename: Susana
authors.initials: S
authors.lastname: Castañón
authors.forename: Matti
authors.initials: M
authors.lastname: Sällberg
authors.forename: Geert
authors.initials: G
authors.lastname: Leroux-Roels
authors.forename: Ola
authors.initials: O
authors.lastname: Weiland
authors.forename: Margarita
authors.initials: M
authors.lastname: Pardo
authors.forename: Vicente
authors.initials: V
authors.lastname: Carreño
mesh_terms: D000328:Adult; D000410:Alanine Transaminase / Q000097:blood*; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D002455:Cell Division / Q000276:immunology; D002478:Cells, Cultured; D005260:Female; D019698:Hepatitis C, Chronic / Q000097:blood / Q000276:immunology*; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D016753:Interleukin-10 / Q000096:biosynthesis; D008099:Liver / Q000166:cytology / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D019562:Viral Load; D014766:Viremia / Q000097:blood / Q000276:immunology
chemical_list: D016753:Interleukin-10; D007371:Interferon-gamma; D000410:Alanine Transaminase