Activation of Vγ9Vδ2 T cells by non-peptidic antigens induces the inhibition of subgenomic HCV replication

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Abstract

Hepatitis C virus (HCV) has evolved complex strategies to evade host immune responses and establish chronic infection. Since human Vγ9Vδ2 T lymphocytes play a critical role in the immune response against viruses, we analyzed their antiviral functions on Huh7 hepatoma cells carrying the subgenomic HCV replicon (Rep60 cells). In a transwell culture system, Rep60 cells were co-cultured with either PBMCs or highly purified γδ T cells stimulated by non-peptidic antigens. Vγ9Vδ2 T cell activation was associated with a dramatic reduction of HCV RNA levels. Neutralizing antibodies targeting IFN-γ revealed a critical role for this cytokine in the inhibition of HCV replication. Interestingly, drugs already in clinical use, such as Phosphostim and Zoledronate, known to activate γδ T cells, were shown to induce the inhibition of HCV replication mediated by Vγ9Vδ2 T cells of HCV patients. Our data suggest that the therapeutic activation of Vγ9Vδ2 T lymphocytes may represent an additional strategy to inhibit HCV replication and to restore a Th1-oriented immune response in HCV-infected patients.

Original languageEnglish
Pages (from-to)11-18
Number of pages8
JournalInternational Immunology
Volume18
Issue number1
DOIs
Publication statusPublished - Jan 2006

Keywords

  • γδ T cells
  • Hepatitis C
  • IFN-γ
  • Natural immunity

ASJC Scopus subject areas

  • Immunology

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