In:
Journal of Virology, American Society for Microbiology, Vol. 78, No. 11 ( 2004-06), p. 5707-5719
Abstract:
The cytotoxic T-cell response in chronic hepatitis B virus (HBV) infection has been described as weak and mono- or oligospecific in comparison to the more robust virus-specific T-cell response present in resolved infection. However, chronic hepatitis B is a heterogeneous disease with markedly variable levels of virus replication and liver disease activity. Here we analyzed (both directly ex vivo and after in vitro stimulation) the HBV-specific CD8 T-cell responses against structural and nonstructural HBV proteins longitudinally in patients with different patterns of chronic infections. We found that the profiles of virus-specific CD8 + -T-cell responses during chronic infections are highly heterogeneous and influenced more by the level of HBV replication than by the activity of liver disease. An HBV DNA load of 〈 10 7 copies/ml appears to be the threshold below which circulating multispecific HBV-specific CD8 + T cells are consistently detected. Furthermore, CD8 + T cells with different specificities are differentially regulated during chronic infections. HBV core-specific CD8 + T cells are associated with viral control, while CD8 + T cells specific for envelope and polymerase epitopes can occasionally be found in the setting of high levels ( 〉 10 7 copies) of HBV replication. These findings have implications for the design of immunotherapy for chronic HBV infections.
Type of Medium:
Online Resource
ISSN:
0022-538X
,
1098-5514
DOI:
10.1128/JVI.78.11.5707-5719.2004
Language:
English
Publisher:
American Society for Microbiology
Publication Date:
2004
detail.hit.zdb_id:
1495529-5
Permalink