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BukuThe 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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