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

Chiara Agrati, Tonino Alonzi, Rafaella De Santis, Concetta Castilletti, Isabella Abbate, Maria Rosaria Capobianchi, Gianpiero D'Offizi, Francesca Siepi, Gian Maria Fimia, Marco Tripodi, Fabrizio Poccia

Research output: Contribution to journalArticlepeer-review

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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