Interferon-α Improves Phosphoantigen-Induced Vγ9Vδ2 T-Cells Interferon-γ Production during Chronic HCV Infection
| Autor: | Chiara Agrati, Hélène Sicard, Maria Rosaria Capobianchi, Giulia Berno, Alessandra Sacchi, Veronica Bordoni, Federico Martini, Cristiana Gioia, Gianpiero D'Offizi, Ubaldo Visco Comandini, Eleonora Lalle, Chrysoula Vlassi, Eleonora Cimini, Cecile Bonnafous |
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| Přispěvatelé: | Cimini, E., Bonnafous, C., Bordoni, V., Lalle, E., Sicard, H., Sacchi, A., Berno, G., Gioia, C., D'Offizi, G., Visco Comandini, U., Vlassi, C., Capobianchi, M. R., Martini, F., Agrati, C. |
| Rok vydání: | 2012 |
| Předmět: |
Adult
Male Hepatitis C virus T-Lymphocytes Immune Cells Immunology Alpha interferon lcsh:Medicine Stimulation Viral diseases Biology medicine.disease_cause Lymphocyte Activation Antiviral Agents Hepatitis Immunomodulation Interferon-gamma Immune system In vivo medicine Animals Humans Interferon gamma lcsh:Science Aged Multidisciplinary Tumor Necrosis Factor-alpha T Cells lcsh:R Immunity Interferon-alpha Hepatitis C Chronic Middle Aged Hepatitis C In vitro Innate Immunity Macaca fascicularis Immune System Cytokines Medicine Infectious diseases Tumor necrosis factor alpha lcsh:Q Female Clinical Immunology medicine.drug Research Article |
| Zdroj: | PLoS ONE PLoS ONE, Vol 7, Iss 5, p e37014 (2012) |
| ISSN: | 1932-6203 |
| DOI: | 10.1371/journal.pone.0037014 |
| Popis: | In chronic HCV infection, treatment failure and defective host immune response highly demand improved therapy strategies. Vγ9Vδ2 T-cells may inhibit HCV replication in vitro through IFN-γ release after Phosphoantigen (PhAg) stimulation. The aim of our work was to analyze Vγ9Vδ2 T-cell functionality during chronic HCV infection, studying the role of IFN-α on their function capability. IFN-γ production by Vγ9Vδ2 T-cells was analyzed in vitro in 24 HCV-infected patients and 35 healthy donors (HD) after PhAg stimulation with or without IFN-α. The effect of in vivo PhAg/IFN-α administration on plasma IFN-γ levels was analyzed in M. fascicularis monkeys. A quantitative analysis of IFN-γ mRNA level and stability in Vγ9Vδ2 T-cells was also evaluated. During chronic HCV infection, Vγ9Vδ2 T-cells showed an effector/activated phenotype and were significantly impaired in IFN-γ production. Interestingly, IFN-α was able to improve their IFN-γ response to PhAg both in vitro in HD and HCV-infected patients, and in vivo in Macaca fascicularis primates. Finally, IFN-α increased IFN-γ-mRNA transcription and stability in PhAg-activated Vγ9Vδ2 T-cells. Altogether our results show a functional impairment of Vγ9Vδ2 T-cells during chronic HCV infection that can be partially restored by using IFN-α. A study aimed to evaluate the antiviral impact of PhAg/IFN-α combination may provide new insight in designing possible combined strategies to improve HCV infection treatment outcome. © 2012 Cimini et al. |
| Databáze: | OpenAIRE |
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