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

• Published in: International immunology 2006-01, Vol.18 (1), p.11-18
• Main Authors: Agrati, Chiara, Alonzi, Tonino, De Santis, Rafaella, Castilletti, Concetta, Abbate, Isabella, Capobianchi, Maria Rosaria, D'Offizi, Gianpiero, Siepi, Francesca, Fimia, Gian Maria, Tripodi, Marco, Poccia, Fabrizio
• Format: Article
• Language: English
• Subjects: Hepatitis C virus
• ISSN: 0953-8178; 1460-2377
• DOI: 10.1093/intimm/dxh337

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 T sub(h)1-oriented immune response in HCV-infected patients.