title: In vivo interferon-alpha/ribavirin treatment modulates Vγ9Vδ2 T-cell function during chronic HCV infection.
abstract: In chronic hepatitis C virus (HCV) infection, treatment failure and defective host immune response highly demand improved therapy strategies. Vγ9Vδ2 T-cells represent a good target for HCV immunotherapy, since phosphoantigen (PhAg)-activated Vγ9Vδ2 T-lymphocytes are able to inhibit subgenomic HCV replication by interferon (IFN)-γ release. A profound impairment of IFN-γ production by Vγ9Vδ2 T-cells during chronic HCV infection was previously shown. Interestingly, in vitro IFN-α partially restored Vγ9Vδ2 T-cells responsiveness to PhAg, by stabilizing IFN-γ-mRNA. To verify how in vivo IFN-α/ribavirin (RBV) treatment could affect Vγ9Vδ2 T-cells phenotype and responsiveness to PhAg in HCV-infected patients, 10 subjects underwent a longitudinal study before and after treatment. IFN-α/RBV therapy did not significantly modify Vγ9Vδ2 T-cell numbers and differentiation profile. Interestingly, Vγ9Vδ2 T-cell responsiveness remained unmodified until 3 weeks of therapy, but dropped after 1 month, suggesting that repeated in vivo IFN-α administration in the absence of T-cell receptor (TCR)-mediated signals results in Vγ9Vδ2 T-cell anergy. The present work defines the window of possible application of combined strategies targeting Vγ9Vδ2 T-cells during chronic HCV infection; specifically, the first 3 weeks from the beginning of treatment may represent the optimal time to target Vγ9Vδ2 T-cells in vivo, since their function in terms of IFN-γ production is preserved.
authors: Cellular Immunology Laboratory, INMI L. Spallanzani, Rome, Italy.
authors: Eleonora
authors: E
authors: Cimini
authors: Cécile
authors: C
authors: Bonnafous
authors: Helene
authors: H
authors: Sicard
authors: Chrysoula
authors: C
authors: Vlassi
authors: Gianpiero
authors: G
authors: D'Offizi
authors: Maria R
authors: MR
authors: Capobianchi
authors: Federico
authors: F
authors: Martini
authors: Chiara
authors: C
authors: Agrati
mesh_terms: D000328:Adult; D000998:Antiviral Agents / Q000008:administration & dosage*; D017635:Clonal Anergy / Q000187:drug effects* / Q000276:immunology; D005260:Female; D016174:Hepacivirus / Q000276:immunology*; D019698:Hepatitis C, Chronic / Q000188:drug therapy / Q000276:immunology / Q000473:pathology; D006801:Humans; D016898:Interferon-alpha / Q000008:administration & dosage*; D007371:Interferon-gamma / Q000276:immunology; D008297:Male; D008875:Middle Aged; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000276:immunology*; D012254:Ribavirin / Q000008:administration & dosage*; D013997:Time Factors
chemical_list: D000998:Antiviral Agents; C573415:IFNG protein, human; D016898:Interferon-alpha; D016692:Receptors, Antigen, T-Cell, gamma-delta; D012254:Ribavirin; D007371:Interferon-gamma