Bim-mediated apoptosis and PD-1/PD-L1 pathway impair reactivity of PD1+/CD127- HCV-specific CD8+ cells targeting the virus in chronic hepatitis C virus infection
Authors
Larrubia Marfil, Juan Ramón; Benito Martínez, Selma; Miquel Plaza, Joaquin; Calvino Fernández, Mirian; Sanz De Villalobos , Eduardo; [et al.]Identifiers
Permanent link (URI): http://hdl.handle.net/10017/59265DOI: 10.1016/j.cellimm.2011.03.011
ISSN: 0008-8749
Date
2011Affiliation
Universidad de Alcalá. Departamento de MedicinaFunders
Junta de Comunidades de Castilla-La Mancha
Fundación de Investigación Médica Mutua Madrileña
Instituto de Salud Carlos III
Asociación de Hepatología Translacional
Bibliographic citation
Cellular Immunology, 2011, v. 269, n. , p. 104-114
Keywords
HCV
Viral persistence
PD-1
CD127 PD-L1
z-VAD-fmk
Bim
Chronic hepatitis
Apoptosis
Cytotoxic T lymphocytes
Description / Notes
26 p.
Project
info:eu-repo/grantAgreement/JCCM/Fiscam/PI-2007%32/ES//
info:eu-repo/grantAgreement/FMM//2548%2008/ES//
info:eu-repo/grantAgreement/ISC III//CA07%00157/ES//
info:eu-repo/grantAgreement/AHTl//AHT10%01/ES//
Document type
info:eu-repo/semantics/article
Version
info:eu-repo/semantics/acceptedVersion
Rights
Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)
Access rights
info:eu-repo/semantics/openAccess
Abstract
PD-1 molecule promotes anergy and IL-7 receptor (CD127) induces an anti-apoptotic effect on T cells. Correlation between PD-1/CD127 phenotype and hepatitis C virus (HCV)-specific CD8+ cell reactivity in resolved infection (RI) after treatment and persistent HCV-infection (PI) was analysed. Directly ex vivo, PD-1 and CD127 expression on HCV-specific CD8+ cells displayed a positive and negative correlation, respectively with viraemia. Proliferation after stimulation on PD-1/CD127+ cells from RI cases was preserved, while it was impaired on PD-1+/CD127 cells from PI patients. PD1+/CD127+ population was observed in PI, and these maintained expansion ability but they did not target the virus. Frequency of PI cases with HCV-specific CD8+ cell proliferation increased after anti-PD-L1 and anti-apoptotic treatment. Bim expression on HCV-specific CD8+ cells from PI patients was enhanced. In conclusion, during chronic HCV infection non-reactive HCV-specific CD8+ cells targeting the virus are PD-1+/CD127/Bim+ and, blocking apoptosis and PD-1/PD-L1 pathway on them enhances in vitro reactivity.
Files in this item
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bim_larrubia_CI_2011.pdf | 1.475Mb |
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bim_larrubia_CI_2011.pdf | 1.475Mb |
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