Restoration of HCV-specific CD8+ T cell function by interferon-free therapy
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, I...
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| Main Authors: | , , , , , , , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
[2014]
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| In: |
Journal of hepatology
Year: 2014, Volume: 61, Issue: 3, Pages: 538-543 |
| ISSN: | 1600-0641 |
| DOI: | 10.1016/j.jhep.2014.05.043 |
| Online Access: | Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1016/j.jhep.2014.05.043 Verlag, lizenzpflichtig, Volltext: http://www.sciencedirect.com/science/article/pii/S0168827814003912 
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| Author Notes: | Bianca Martin, Nadine Hennecke, Volker Lohmann, Antonin Kayser, Christoph Neumann-Haefelin, George Kukolj, Wulf-Otto Böcher, Robert Thimme |
| Summary: | 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 4weeks 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. |
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| Item Description: | Gesehen am 16.09.2020 |
| Physical Description: | Online Resource |
| ISSN: | 1600-0641 |
| DOI: | 10.1016/j.jhep.2014.05.043 |