Partial restoration of immune response in Hepatitis C patients after viral clearance by direct-acting antiviral therapy
Llorens-Revull, Meritxell (Universitat Autònoma de Barcelona)
Costafreda Salvany, Maria Isabel (Banc de Sang i Teixits (Barcelona, Catalunya))
Rico, Angie (Banc de Sang i Teixits (Barcelona, Catalunya))
Guerrero Murillo, Mercedes (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Soria, Maria Eugenia (Universidad Autónoma de Madrid)
Píriz-Ruzo, Sofía (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Vargas-Accarino, Elena (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Gabriel-Medina, Pablo (Hospital Universitari Vall d'Hebron)
Rodríguez Frías, Francisco (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Riveiro Barciela, Mar (Hospital Universitari Vall d'Hebron)
Perales Viejo, Celia (Universidad Autónoma de Madrid)
Quer, Josep 1963- (Universitat Autònoma de Barcelona)
Sauleda, Silvia (Banc de Sang i Teixits (Barcelona, Catalunya))
Esteban Mur, Juan Ignacio (Hospital Universitari Vall d'Hebron)
Bes, Marta (Banc de Sang i Teixits (Barcelona, Catalunya))

Data:	2021
Resum:	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.
Ajuts:	Instituto de Salud Carlos III CP14/00121 Instituto de Salud Carlos III CPII19/00001 Instituto de Salud Carlos III PI16/00337 Instituto de Salud Carlos III PI18/00210 Instituto de Salud Carlos III PI19/00301
Drets:	Aquest 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.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Publicat a:	PloS one, Vol. 16 (july 2021) , ISSN 1932-6203

DOI: 10.1371/journal.pone.0254243
PMID: 34242330

18 p, 2.7 MB

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