期刊
JOURNAL OF HEPATOLOGY
卷 61, 期 3, 页码 538-543出版社
ELSEVIER
DOI: 10.1016/j.jhep.2014.05.043
关键词
Hepatitis C virus; DAA; Antiviral therapy; T cell exhaustion; T cell restoration; Immune response
资金
- Deutsche Forschungsgemeinschaft [TH 719/3-2]
- Bundesministerium fur Bildung und Forschung [BMBF 01KI1008H]
- FOR1202 TP2 [TH 719/4-2]
Background & Aims: Chronic hepatitis C virus (HCV) infection is characterised by a failure of virus-specific CD8+ T cells that is mainly caused by viral escape and T cell exhaustion. Constant antigen stimulation has been suggested to contribute to HCV-specific CD8+ T cell exhaustion. However, IFN-based therapies failed to recover HCV-specific CD8+ T cell function suggesting that the damage to CD8+ T cells may be permanent even after antigen removal. It was therefore the objective of this study to analyse the impact of inhibition of ongoing viral replication by IFN-free therapy with direct acting antivirals (DAA) on the phenotype and function of HCV-specific CD8+ T cells. Methods: Virus-specific CD8+ T cells obtained from a patient cohort of 51 previously untreated chronically infected patients undergoing IFN-free therapy with a combination of faldaprevir (a protease inhibitor) and deleobuvir (a non-nucleoside polymerase inhibitor) with or without ribavirin were analysed ex vivo and after in vitro expansion at baseline, wk4, wk12, and after treatment. Results: Our results show the rapid restoration of proliferative HCV-specific CD8+ T cells in the majority of patients with SVR12 within 4 weeks of therapy suggesting that IFN-free therapy mediated antigen removal may restore CD8+ T cell function. Conclusions: This study indicates a specific restoration of proliferative HCV-specific CD8+ T cells under IFN-free therapy. This is in contrast to PegIFN-based therapies that have been shown not to restore T cell function during and after chronic infection. (C) 2014 European Association for the Study of the Liver. Published by Elsevier B. V. All rights reserved.
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