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International Immunology Advance Access originally published online on December 16, 2005
International Immunology 2006 18(1):11-18; doi:10.1093/intimm/dxh337
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© The Japanese Society for Immunology. 2005. All rights reserved. For permissions, please e-mail: journals.permissions@oxfordjournals.org

Activation of V{gamma}9V{delta}2 T cells by non-peptidic antigens induces the inhibition of subgenomic HCV replication

Chiara Agrati1,*, Tonino Alonzi1,*, Rafaella De Santis1, Concetta Castilletti1, Isabella Abbate1, Maria Rosaria Capobianchi1, Gianpiero D'Offizi1, Francesca Siepi1, Gian Maria Fimia1, Marco Tripodi1,2 and Fabrizio Poccia1

1 Laboratory of Cellular Immunology, Laboratory of Gene Expression, Laboratory of Virology, Clinical Department, National Institute for Infectious Diseases "Lazzaro Spallanzani"—IRCCS, Via Portuense 292, 00149 Rome, Italy
2 Dipartimento di Biotecnologie Cellulari ed Ematologia, Sezione di Genetica Molecolare, Istituto Pasteur-Fondazione Cenci Bolognetti, University of Rome ‘La Sapienza’, 00161 Rome, Italy

Correspondence to: F. Poccia; E-mail: poccia{at}inmi.it

Hepatitis C virus (HCV) has evolved complex strategies to evade host immune responses and establish chronic infection. Since human V{gamma}9V{delta}2 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 {gamma}{delta} T cells stimulated by non-peptidic antigens. V{gamma}9V{delta}2 T cell activation was associated with a dramatic reduction of HCV RNA levels. Neutralizing antibodies targeting IFN-{gamma} 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 {gamma}{delta} T cells, were shown to induce the inhibition of HCV replication mediated by V{gamma}9V{delta}2 T cells of HCV patients. Our data suggest that the therapeutic activation of V{gamma}9V{delta}2 T lymphocytes may represent an additional strategy to inhibit HCV replication and to restore a Th1-oriented immune response in HCV-infected patients.

Keywords: hepatitis C, IFN-{gamma}, natural immunity, {gamma}{delta} T cells

* These authors contributed equally to this work.

Transmitting editor: E. Vivier


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