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The viral clearance in interferon-treated chronic hepatitis C is associated with increased cytotoxic T cell frequencies (from Journal of Hepatology 1999, 31, 407-415)
Bibliografi
Author:
Lohr, Hanns F.
;
Schmitz, Daniel
;
Arenz, Monika
;
Weyer, Sandra
;
Gerken, Guido
;
Buschenfelde, Karl-Hermann Meyer zum
Topik:
Cellular immune response
;
CTL frequency analysis
;
Cytotoxic T cells
;
ELISPCYD Hepatitis C virus
;
Interferon-a
;
Viral clearance
;
Validation ref - 6
;
8
Bahasa:
(EN )
Penerbit:
European Association for the Study of Liver
Tahun Terbit:
1999
Jenis:
Article - diterbitkan di jurnal ilmiah internasional
Fulltext:
lhr1999.pdf
(1.05MB;
0 download
)
Abstract
Background/Aims: Cytotoxic T lymphocytes have
been demonstrated in peripheral blood and liver tissue of patients with chronic hepatitis C virus infection, but their signitlcance for viral clearance is unknown. Therefore, we analyzed hepatitis C virus-specific cytotoxic T lymphocyte precursor frequencies in chronic hepatitis C virus carriers during interferon-a treatment.
Methods: Blood mononuclear cells or CDS+ T cells
from HLA-A2 positive and negative patients and controls were analyzed in chromium-release assays using a panel of 18 synthetic peptides from the HCV core, El and NS4 antigens bearing HLA-A2 binding motifs. Specific cytotoxic T lymphocyte precursor frequencies were studied within CDS+ T cells derived from interferon-a-treated patients using a TNF-abased ELISPOT assay and compared to viremia levels.
Results: T cells from 16 of 24 HLA-AZ+ but none of
the six IDA-AZ- patients with chronic hepatitis C
and six HLA-A2+ healthy controls lysed targets pulsed with peptide cocktails. Fine specificity revealed four very immunogenic epitopes in the core (C36-44, Cl32140) and the envelope regions (E332-340, E363-372). Cytotoxic T lymphocyte precursor frequencies were prospectively analyzed in 11 interferon-(alpha)-treated HLA-AZ+ hepatitis C virus patients. Four sustained and two transient therapy responders showed lower pretreatment viremia levels and signiticantly higher specific cytotoxic T lymphocyte precursor frequencies during viral clearance compared to five therapy non-responders and untreated controls. Conclusions: The quantitative induction of HLA-class I restricted responses by interferon-a could contribute to a beneficial outcome of hepatitis C virus infections. Furthermore, it appears that the balance between viral load and specitlc cellular immune responses is critical for successful viral clearance.
[validation ref - 6, 8]
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