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In vivo interferon-alpha/ribavirin treatment modulates Vγ9Vδ2 T-cell function during chronic HCV infection
- Source :
- Journal of interferoncytokine research : the official journal of the International Society for Interferon and Cytokine Research. 33(3)
- Publication Year :
- 2013
-
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.
- Subjects :
- Adult
Male
Time Factors
medicine.medical_treatment
T cell
Immunology
Alpha interferon
Hepacivirus
Antiviral Agents
Virus
chemistry.chemical_compound
Interferon-gamma
Immune system
In vivo
Interferon
Virology
Ribavirin
Medicine
Humans
Clonal Anergy
business.industry
Interferon-alpha
Receptors, Antigen, T-Cell, gamma-delta
Cell Biology
Immunotherapy
Hepatitis C, Chronic
Middle Aged
medicine.anatomical_structure
chemistry
Female
business
medicine.drug
Subjects
Details
- ISSN :
- 15577465
- Volume :
- 33
- Issue :
- 3
- Database :
- OpenAIRE
- Journal :
- Journal of interferoncytokine research : the official journal of the International Society for Interferon and Cytokine Research
- Accession number :
- edsair.doi.dedup.....284c030ee8b9e172d4616341f89cb698