The role of CCR5/CXCR3 expressing CD8+ cells in liver damage and viral control during persistent hepatitis C virus infection
Authors
Larrubia Marfil, Juan Ramón; Calvino Fernández, Mirian; Benito Martínez, Selma; Sanz De Villalobos , Eduardo; Perna Monroy, Luis Cristian; [et al.]Identifiers
Permanent link (URI): http://hdl.handle.net/10017/59287DOI: 10.1016/j.jhep.2007.04.009
ISSN: 0168-8278
Date
2007Affiliation
Universidad de Alcalá. Departamento de Especialidades Médicas; Universidad de Alcalá. Departamento de MedicinaFunders
Schering-Plough-Spain
Junta de Comunidades de Castilla-La Mancha
Bibliographic citation
Journal of Hepatology, 2007, v. 47, n. , p. 632-664
Keywords
Hepatitis C virus
Chemokine receptors
CCR5
CXCR3
Chemokines
CCL3
CXCL10
Chemotaxis
Liver damage
Viral escape mechanism
Description / Notes
20 p.
Project
info:eu-repo/grantAgreement/JCCM/Fiscam/FISCAM%03017-00/ES//
Document type
info:eu-repo/semantics/article
Version
info:eu-repo/semantics/acceptedVersion
Rights
Attribution 4.0 International (CC BY 4.0)
Access rights
info:eu-repo/semantics/openAccess
Abstract
Background/Aims:CXCR3 and CCR5 play a major role in recruiting cytotoxic T cells (Tc) and secreting secondary type 1 cytokines (Tc1) in the liver. HCV could impair their expression as a survival mechanism. The role of these chemokine receptors on CD8+ cells in chronic hepatitis C is analysed. Methods:Serum, chemokines, peripheral blood and intrahepatic lymphocytes from chronic hepatitis C patients were studied. CXCR3 / CCR5 expressing CD8+ cells were quantified by flow-cytometry. Serum chemokines concentration (CXCL10/CCL3) was measured by ELISA. Basal data were correlated with liver inflammation. Longitudinal data were obtained during treatment and correlated with virologic response. Results:CCR5/CXCR3 expressing CD8+ cells were enriched in the liver and correlated with inflammation. Chronic HCV patients presented the same frequency of CCR5high/CXCR3high expressing CD8+ cells in peripheral blood as in healthy controls but higher serum concentration of CXCL10/CCL3. Treatment with PEG-interferon a-2b plus ribavirin increased CCR5high/CXCR3high expressing CD8+ cells frequency in peripheral blood and decreased CXCL10/CCL3 serum concentration. Increase in CXCR3high expressing CD8+ cells after 24 weeks of treatment was correlated with SVR. Conclusions:In chronic hepatitis C, anti-viral treatment induces an increase in CD8+ cells expressing chemokine receptors associated with Tc1 response and a reduction in their ligands. Achievement of viral control is associated with an increase in CXCR3high expressing CD8+ cells during treatment
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role_larrubia_JHEP_2007.pdf | 965.9Kb |
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