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.
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.
Rico
Miguel A
MA
Institute of Hepatology, Hospital Pardo de Aravaca, Madrid, Spain.
Quiroga
Juan A
JA
Subirá
Dolores
D
Garcia
Esteban
E
Castañón
Susana
S
Sällberg
Matti
M
Leroux-Roels
Geert
G
Weiland
Ola
O
Pardo
Margarita
M
Carreño
Vicente
V
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
D016753:Interleukin-10; D007371:Interferon-gamma; D000410:Alanine Transaminase