Interferon-α improves phosphoantigen-induced Vγ9Vδ2 T-cells interferon-γ production during chronic HCV infection

• Published in: PloS one 2012-05, Vol.7 (5), p.e37014-e37014
• Main Authors: Cimini, Eleonora, Bonnafous, Cécile, Bordoni, Veronica, Lalle, Eleonora, Sicard, Helene, Sacchi, Alessandra, Berno, Giulia, Gioia, Cristiana, D'Offizi, Gianpiero, Visco Comandini, Ubaldo, Vlassi, Chrysoula, Capobianchi, Maria Rosaria, Martini, Federico, Agrati, Chiara
• Format: Article
• Language: English
• Subjects: Adult; Aged; Animals; Antigens; Antiviral Agents - pharmacology; Antiviral Agents - therapeutic use; Biology; Chronic infection; Cloning; Cytokines; Drug resistance; Effector cells; Ethics; Experiments; Female; Flow cytometry; Genotype & phenotype; Hepatitis; Hepatitis C, Chronic - drug therapy; Hepatitis C, Chronic - immunology; Humans; Immune response; Immune system; Immunology; Immunotherapy; Infections; Infectious diseases; Interferon; Interferon-alpha - pharmacology; Interferon-alpha - therapeutic use; Interferon-gamma - biosynthesis; Laboratories; Lymphocyte Activation - drug effects; Lymphocyte Activation - immunology; Lymphocytes; Lymphocytes T; Macaca fascicularis; Male; Medicine; Middle Aged; Monkeys; mRNA stability; Patients; Primates; Prostate cancer; Quantitative analysis; RNA polymerase; Stability analysis; Stimulation; T-Lymphocytes - drug effects; T-Lymphocytes - immunology; Transcription; Transcription factors; Tumor Necrosis Factor-alpha - biosynthesis; Tumors; Viral infections; Virology; γ-Interferon
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0037014

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.