The role of CCR5/CXCR3 expressing CD8+ cells in liver damage and viral control during persistent hepatitis C virus infection
Autor: | Jaime Pérez-Hornedo, S. Benito, A. Bienvenido, S. García-Garzón, Fernando González-Mateos, Trinidad Parra, Juan Ramón Larrubia, Cristian Perna, M. Calvino, E. Sanz-de-Villalobos |
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Rok vydání: | 2007 |
Předmět: |
Adult
Male Chemokine Receptors CXCR3 Genotype Receptors CCR5 Hepatitis C virus Inflammation Hepacivirus CD8-Positive T-Lymphocytes Biology Lymphocyte Activation CXCR3 medicine.disease_cause Chemokine receptor immune system diseases medicine Humans Cytotoxic T cell CXCL10 Chemokine CCL3 Cell Death Hepatology Interferon-alpha virus diseases hemic and immune systems Hepatitis C Middle Aged medicine.disease Up-Regulation Chemokine CXCL10 Liver Chronic Disease Immunology biology.protein Cytokines Female medicine.symptom T-Lymphocytes Cytotoxic |
Zdroj: | Journal of Hepatology. 47:632-641 |
ISSN: | 0168-8278 |
Popis: | 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 CCR5 high /CXCR3 high expressing CD8+ cells in peripheral blood as in healthy controls but higher serum concentration of CXCL10/CCL3. Treatment with PEG-interferon α-2b plus ribavirin increased CCR5 high /CXCR3 high expressing CD8+ cells frequency in peripheral blood and decreased CXCL10/CCL3 serum concentration. Increase in CXCR3 high 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 CXCR3 high expressing CD8+ cells during treatment. |
Databáze: | OpenAIRE |
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