Restoration of HCV-specific CD8+ T cell function by interferon-free therapy

• Verfasst von: Martin, Bianca [VerfasserIn]
• Verfasst von: Hennecke, Nadine [VerfasserIn]
• Verfasst von: Lohmann, Volker [VerfasserIn]
• Verfasst von: Kayser, Antonin [VerfasserIn]
• Verfasst von: Neumann-Haefelin, Christoph [VerfasserIn]
• Verfasst von: Kukolj, George [VerfasserIn]
• Verfasst von: Böcher, Wulf-Otto [VerfasserIn]
• Verfasst von: Thimme, Robert [VerfasserIn]
• Titel: Restoration of HCV-specific CD8+ T cell function by interferon-free therapy
• Verf.angabe: Bianca Martin, Nadine Hennecke, Volker Lohmann, Antonin Kayser, Christoph Neumann-Haefelin, George Kukolj, Wulf-Otto Böcher, Robert Thimme
• E-Jahr: 2014
• Jahr: [2014]
• Umfang: 6 S.
• Illustrationen: Diagramme
• Fussnoten: Gesehen am 16.09.2020
• Titel Quelle: Enthalten in: Journal of hepatology
• Ort Quelle: Amsterdam [u.a.] : Elsevier Science, 1985
• Jahr Quelle: 2014
• Band/Heft Quelle: 61(2014), 3, Seite 538-543
• ISSN Quelle: 1600-0641
• DOI: doi:10.1016/j.jhep.2014.05.043
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: Antiviral therapy
• Sach-SW: DAA
• Sach-SW: Hepatitis C virus
• Sach-SW: Immune response
• Sach-SW: T cell exhaustion
• Sach-SW: T cell restoration
• K10plus-PPN: 1733162968

Abstract

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.