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

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 whe...

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Autores: Llorens-Revull, Meritxell|||0000-0002-8671-8907, Costafreda Salvany, Maria Isabel|||0000-0002-3114-3034, Rico, Angie, Guerrero Murillo, Mercedes|||0000-0002-5556-2460, Soria, Maria Eugenia, Píriz-Ruzo, Sofía, Vargas-Accarino, Elena|||0000-0002-2521-0368, Gabriel-Medina, Pablo|||0000-0003-3079-6364, Rodríguez Frías, Francisco|||0000-0002-9128-7013, Riveiro Barciela, Mar|||0000-0001-9309-2052, Perales Viejo, Celia|||0000-0003-1618-1937, Quer, Josep|||0000-0003-0014-084X, Sauleda, Silvia|||0000-0001-7343-9557, Esteban Mur, Juan Ignacio|||0000-0001-5085-917X, Bes, Marta|||0000-0001-6103-072X
Tipo de recurso: artículo
Fecha de publicación:2021
País:España
Institución:Universitat Autònoma de Barcelona
Repositorio:Dipòsit Digital de Documents de la UAB
Idioma:inglés
OAI Identifier:oai:ddd.uab.cat:256494
Acceso en línea:https://ddd.uab.cat/record/256494
https://dx.doi.org/urn:doi:10.1371/journal.pone.0254243
Access Level:acceso abierto
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spelling Partial restoration of immune response in Hepatitis C patients after viral clearance by direct-acting antiviral therapyLlorens-Revull, Meritxell|||0000-0002-8671-8907Costafreda Salvany, Maria Isabel|||0000-0002-3114-3034Rico, AngieGuerrero Murillo, Mercedes|||0000-0002-5556-2460Soria, Maria EugeniaPíriz-Ruzo, SofíaVargas-Accarino, Elena|||0000-0002-2521-0368Gabriel-Medina, Pablo|||0000-0003-3079-6364Rodríguez Frías, Francisco|||0000-0002-9128-7013Riveiro Barciela, Mar|||0000-0001-9309-2052Perales Viejo, Celia|||0000-0003-1618-1937Quer, Josep|||0000-0003-0014-084XSauleda, Silvia|||0000-0001-7343-9557Esteban Mur, Juan Ignacio|||0000-0001-5085-917XBes, Marta|||0000-0001-6103-072XHCV 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. 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. 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. 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. 22021-01-0120212021-01-01Articlehttp://purl.org/coar/resource_type/c_6501VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttps://ddd.uab.cat/record/256494https://dx.doi.org/urn:doi:10.1371/journal.pone.0254243reponame:Dipòsit Digital de Documents de la UABinstname:Universitat Autònoma de BarcelonaInglésengMinisterio de Economía y Competitividad https://doi.org/10.13039/501100003329 CP14/00121Instituto de Salud Carlos III https://doi.org/10.13039/501100004587 CPII19/00001Ministerio de Economía y Competitividad https://doi.org/10.13039/501100003329 PI16/00337Instituto de Salud Carlos III https://doi.org/10.13039/501100004587 PI18/00210Instituto de Salud Carlos III https://doi.org/10.13039/501100004587 PI19/00301open accesshttp://purl.org/coar/access_right/c_abf2Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.https://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:ddd.uab.cat:2564942026-06-06T12:50:31Z
dc.title.none.fl_str_mv Partial restoration of immune response in Hepatitis C patients after viral clearance by direct-acting antiviral therapy
title Partial restoration of immune response in Hepatitis C patients after viral clearance by direct-acting antiviral therapy
spellingShingle Partial restoration of immune response in Hepatitis C patients after viral clearance by direct-acting antiviral therapy
Llorens-Revull, Meritxell|||0000-0002-8671-8907
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
dc.creator.none.fl_str_mv Llorens-Revull, Meritxell|||0000-0002-8671-8907
Costafreda Salvany, Maria Isabel|||0000-0002-3114-3034
Rico, Angie
Guerrero Murillo, Mercedes|||0000-0002-5556-2460
Soria, Maria Eugenia
Píriz-Ruzo, Sofía
Vargas-Accarino, Elena|||0000-0002-2521-0368
Gabriel-Medina, Pablo|||0000-0003-3079-6364
Rodríguez Frías, Francisco|||0000-0002-9128-7013
Riveiro Barciela, Mar|||0000-0001-9309-2052
Perales Viejo, Celia|||0000-0003-1618-1937
Quer, Josep|||0000-0003-0014-084X
Sauleda, Silvia|||0000-0001-7343-9557
Esteban Mur, Juan Ignacio|||0000-0001-5085-917X
Bes, Marta|||0000-0001-6103-072X
author Llorens-Revull, Meritxell|||0000-0002-8671-8907
author_facet Llorens-Revull, Meritxell|||0000-0002-8671-8907
Costafreda Salvany, Maria Isabel|||0000-0002-3114-3034
Rico, Angie
Guerrero Murillo, Mercedes|||0000-0002-5556-2460
Soria, Maria Eugenia
Píriz-Ruzo, Sofía
Vargas-Accarino, Elena|||0000-0002-2521-0368
Gabriel-Medina, Pablo|||0000-0003-3079-6364
Rodríguez Frías, Francisco|||0000-0002-9128-7013
Riveiro Barciela, Mar|||0000-0001-9309-2052
Perales Viejo, Celia|||0000-0003-1618-1937
Quer, Josep|||0000-0003-0014-084X
Sauleda, Silvia|||0000-0001-7343-9557
Esteban Mur, Juan Ignacio|||0000-0001-5085-917X
Bes, Marta|||0000-0001-6103-072X
author_role author
author2 Costafreda Salvany, Maria Isabel|||0000-0002-3114-3034
Rico, Angie
Guerrero Murillo, Mercedes|||0000-0002-5556-2460
Soria, Maria Eugenia
Píriz-Ruzo, Sofía
Vargas-Accarino, Elena|||0000-0002-2521-0368
Gabriel-Medina, Pablo|||0000-0003-3079-6364
Rodríguez Frías, Francisco|||0000-0002-9128-7013
Riveiro Barciela, Mar|||0000-0001-9309-2052
Perales Viejo, Celia|||0000-0003-1618-1937
Quer, Josep|||0000-0003-0014-084X
Sauleda, Silvia|||0000-0001-7343-9557
Esteban Mur, Juan Ignacio|||0000-0001-5085-917X
Bes, Marta|||0000-0001-6103-072X
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
description 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. 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. 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. 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.
publishDate 2021
dc.date.none.fl_str_mv 2
2021-01-01
2021
2021-01-01
dc.type.none.fl_str_mv Article
http://purl.org/coar/resource_type/c_6501
VoR
http://purl.org/coar/version/c_970fb48d4fbd8a85
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv https://ddd.uab.cat/record/256494
https://dx.doi.org/urn:doi:10.1371/journal.pone.0254243
url https://ddd.uab.cat/record/256494
https://dx.doi.org/urn:doi:10.1371/journal.pone.0254243
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.relation.none.fl_str_mv Ministerio de Economía y Competitividad https://doi.org/10.13039/501100003329 CP14/00121
Instituto de Salud Carlos III https://doi.org/10.13039/501100004587 CPII19/00001
Ministerio de Economía y Competitividad https://doi.org/10.13039/501100003329 PI16/00337
Instituto de Salud Carlos III https://doi.org/10.13039/501100004587 PI18/00210
Instituto de Salud Carlos III https://doi.org/10.13039/501100004587 PI19/00301
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
https://creativecommons.org/licenses/by/4.0/
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
https://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.source.none.fl_str_mv reponame:Dipòsit Digital de Documents de la UAB
instname:Universitat Autònoma de Barcelona
instname_str Universitat Autònoma de Barcelona
reponame_str Dipòsit Digital de Documents de la UAB
collection Dipòsit Digital de Documents de la UAB
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repository.mail.fl_str_mv
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