Partial restoration of immune response in Hepatitis C patients after viral clearance by direct-acting antiviral therapy.

<h4>Background & aims</h4>HCV CD4+ and CD8+ specific T cells responses are functionally impaired during chronic hepatitis C infection. DAAs therapies eradicate HCV infection in more than 95% of treated patients. However, the impact of HCV elimination on immune responses remain contro...

Full description

Bibliographic Details
Main Authors: Meritxell Llorens-Revull, Maria Isabel Costafreda, Angie Rico, Mercedes Guerrero-Murillo, Maria Eugenia Soria, Sofía Píriz-Ruzo, Elena Vargas-Accarino, Pablo Gabriel-Medina, Francisco Rodríguez-Frías, Mar Riveiro-Barciela, Celia Perales, Josep Quer, Silvia Sauleda, Juan Ignacio Esteban, Marta Bes
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2021-01-01
Series:PLoS ONE
Online Access:https://doi.org/10.1371/journal.pone.0254243
id doaj-8903af06d6dd4215b78f5bc7dc80815d
record_format Article
spelling doaj-8903af06d6dd4215b78f5bc7dc80815d2021-07-24T04:32:36ZengPublic Library of Science (PLoS)PLoS ONE1932-62032021-01-01167e025424310.1371/journal.pone.0254243Partial restoration of immune response in Hepatitis C patients after viral clearance by direct-acting antiviral therapy.Meritxell Llorens-RevullMaria Isabel CostafredaAngie RicoMercedes Guerrero-MurilloMaria Eugenia SoriaSofía Píriz-RuzoElena Vargas-AccarinoPablo Gabriel-MedinaFrancisco Rodríguez-FríasMar Riveiro-BarcielaCelia PeralesJosep QuerSilvia SauledaJuan Ignacio EstebanMarta Bes<h4>Background & aims</h4>HCV CD4+ and CD8+ specific T cells responses are functionally impaired during chronic hepatitis C infection. DAAs therapies eradicate HCV infection in more than 95% of treated patients. However, the impact of HCV elimination on immune responses remain controversial. Here, we aimed to investigate whether HCV cure by DAAs could reverse the impaired immune response to HCV.<h4>Methods</h4>We analyzed 27 chronic HCV infected patients undergoing DAA treatment in tertiary care hospital, and we determined the phenotypical and functional changes in both HCV CD8+ and CD4+ specific T-cells before and after viral clearance. PD-1, TIM-3 and LAG-3 cell-surface expression was assessed by flow cytometry to determine CD4+ T cell exhaustion. Functional responses to HCV were analyzed by IFN-Ɣ ELISPOT, intracellular cytokine staining (IL-2 and IFN-Ɣ) and CFSE-based proliferation assays.<h4>Results</h4>We observed a significant decrease in the expression of PD-1 in CD4+ T-cells after 12 weeks of viral clearance in non-cirrhotic patients (p = 0.033) and in treatment-naive patients (p = 0.010), indicating a partial CD4 phenotype restoration. IFN-Ɣ and IL-2 cytokines production by HCV-specific CD4+ and CD8+ T cells remained impaired upon HCV eradication. Finally, a significant increase of the proliferation capacity of both HCV CD4+ and CD8+ specific T-cells was observed after HCV elimination by DAAs therapies.<h4>Conclusions</h4>Our results show that in chronically infected patients HCV elimination by DAA treatment lead to partial reversion of CD4+ T cell exhaustion. Moreover, proliferative capacity of HCV-specific CD4+ and CD8+ T cells is recovered after DAA's therapies.https://doi.org/10.1371/journal.pone.0254243
collection DOAJ
language English
format Article
sources DOAJ
author Meritxell Llorens-Revull
Maria Isabel Costafreda
Angie Rico
Mercedes Guerrero-Murillo
Maria Eugenia Soria
Sofía Píriz-Ruzo
Elena Vargas-Accarino
Pablo Gabriel-Medina
Francisco Rodríguez-Frías
Mar Riveiro-Barciela
Celia Perales
Josep Quer
Silvia Sauleda
Juan Ignacio Esteban
Marta Bes
spellingShingle Meritxell Llorens-Revull
Maria Isabel Costafreda
Angie Rico
Mercedes Guerrero-Murillo
Maria Eugenia Soria
Sofía Píriz-Ruzo
Elena Vargas-Accarino
Pablo Gabriel-Medina
Francisco Rodríguez-Frías
Mar Riveiro-Barciela
Celia Perales
Josep Quer
Silvia Sauleda
Juan Ignacio Esteban
Marta Bes
Partial restoration of immune response in Hepatitis C patients after viral clearance by direct-acting antiviral therapy.
PLoS ONE
author_facet Meritxell Llorens-Revull
Maria Isabel Costafreda
Angie Rico
Mercedes Guerrero-Murillo
Maria Eugenia Soria
Sofía Píriz-Ruzo
Elena Vargas-Accarino
Pablo Gabriel-Medina
Francisco Rodríguez-Frías
Mar Riveiro-Barciela
Celia Perales
Josep Quer
Silvia Sauleda
Juan Ignacio Esteban
Marta Bes
author_sort Meritxell Llorens-Revull
title Partial restoration of immune response in Hepatitis C patients after viral clearance by direct-acting antiviral therapy.
title_short Partial restoration of immune response in Hepatitis C patients after viral clearance by direct-acting antiviral therapy.
title_full Partial restoration of immune response in Hepatitis C patients after viral clearance by direct-acting antiviral therapy.
title_fullStr Partial restoration of immune response in Hepatitis C patients after viral clearance by direct-acting antiviral therapy.
title_full_unstemmed Partial restoration of immune response in Hepatitis C patients after viral clearance by direct-acting antiviral therapy.
title_sort partial restoration of immune response in hepatitis c patients after viral clearance by direct-acting antiviral therapy.
publisher Public Library of Science (PLoS)
series PLoS ONE
issn 1932-6203
publishDate 2021-01-01
description <h4>Background & aims</h4>HCV CD4+ and CD8+ specific T cells responses are functionally impaired during chronic hepatitis C infection. DAAs therapies eradicate HCV infection in more than 95% of treated patients. However, the impact of HCV elimination on immune responses remain controversial. Here, we aimed to investigate whether HCV cure by DAAs could reverse the impaired immune response to HCV.<h4>Methods</h4>We analyzed 27 chronic HCV infected patients undergoing DAA treatment in tertiary care hospital, and we determined the phenotypical and functional changes in both HCV CD8+ and CD4+ specific T-cells before and after viral clearance. PD-1, TIM-3 and LAG-3 cell-surface expression was assessed by flow cytometry to determine CD4+ T cell exhaustion. Functional responses to HCV were analyzed by IFN-Ɣ ELISPOT, intracellular cytokine staining (IL-2 and IFN-Ɣ) and CFSE-based proliferation assays.<h4>Results</h4>We observed a significant decrease in the expression of PD-1 in CD4+ T-cells after 12 weeks of viral clearance in non-cirrhotic patients (p = 0.033) and in treatment-naive patients (p = 0.010), indicating a partial CD4 phenotype restoration. IFN-Ɣ and IL-2 cytokines production by HCV-specific CD4+ and CD8+ T cells remained impaired upon HCV eradication. Finally, a significant increase of the proliferation capacity of both HCV CD4+ and CD8+ specific T-cells was observed after HCV elimination by DAAs therapies.<h4>Conclusions</h4>Our results show that in chronically infected patients HCV elimination by DAA treatment lead to partial reversion of CD4+ T cell exhaustion. Moreover, proliferative capacity of HCV-specific CD4+ and CD8+ T cells is recovered after DAA's therapies.
url https://doi.org/10.1371/journal.pone.0254243
work_keys_str_mv AT meritxellllorensrevull partialrestorationofimmuneresponseinhepatitiscpatientsafterviralclearancebydirectactingantiviraltherapy
AT mariaisabelcostafreda partialrestorationofimmuneresponseinhepatitiscpatientsafterviralclearancebydirectactingantiviraltherapy
AT angierico partialrestorationofimmuneresponseinhepatitiscpatientsafterviralclearancebydirectactingantiviraltherapy
AT mercedesguerreromurillo partialrestorationofimmuneresponseinhepatitiscpatientsafterviralclearancebydirectactingantiviraltherapy
AT mariaeugeniasoria partialrestorationofimmuneresponseinhepatitiscpatientsafterviralclearancebydirectactingantiviraltherapy
AT sofiapirizruzo partialrestorationofimmuneresponseinhepatitiscpatientsafterviralclearancebydirectactingantiviraltherapy
AT elenavargasaccarino partialrestorationofimmuneresponseinhepatitiscpatientsafterviralclearancebydirectactingantiviraltherapy
AT pablogabrielmedina partialrestorationofimmuneresponseinhepatitiscpatientsafterviralclearancebydirectactingantiviraltherapy
AT franciscorodriguezfrias partialrestorationofimmuneresponseinhepatitiscpatientsafterviralclearancebydirectactingantiviraltherapy
AT marriveirobarciela partialrestorationofimmuneresponseinhepatitiscpatientsafterviralclearancebydirectactingantiviraltherapy
AT celiaperales partialrestorationofimmuneresponseinhepatitiscpatientsafterviralclearancebydirectactingantiviraltherapy
AT josepquer partialrestorationofimmuneresponseinhepatitiscpatientsafterviralclearancebydirectactingantiviraltherapy
AT silviasauleda partialrestorationofimmuneresponseinhepatitiscpatientsafterviralclearancebydirectactingantiviraltherapy
AT juanignacioesteban partialrestorationofimmuneresponseinhepatitiscpatientsafterviralclearancebydirectactingantiviraltherapy
AT martabes partialrestorationofimmuneresponseinhepatitiscpatientsafterviralclearancebydirectactingantiviraltherapy
_version_ 1721284372615659520