Activation of Vgamma9Vdelta2 T cells by non-peptidic antigens induces the inhibition of subgenomic HCV replication.
Hepatitis C virus (HCV) has evolved complex strategies to evade host immune responses and establish chronic infection. Since human Vgamma9Vdelta2 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 gammadelta T cells stimulated by non-peptidic antigens. Vgamma9Vdelta2 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 gammadelta T cells, were shown to induce the inhibition of HCV replication mediated by Vgamma9Vdelta2 T cells of HCV patients. Our data suggest that the therapeutic activation of Vgamma9Vdelta2 T lymphocytes may represent an additional strategy to inhibit HCV replication and to restore a Th1-oriented immune response in HCV-infected patients.
Agrati
Chiara
C
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.
Alonzi
Tonino
T
De Santis
Rafaella
R
Castilletti
Concetta
C
Abbate
Isabella
I
Capobianchi
Maria Rosaria
MR
D'Offizi
Gianpiero
G
Siepi
Francesca
F
Fimia
Gian Maria
GM
Tripodi
Marco
M
Poccia
Fabrizio
F
D000941:Antigens / Q000276:immunology; D050071:Bone Density Conservation Agents / Q000627:therapeutic use; D002460:Cell Line; D018920:Coculture Techniques; D004164:Diphosphonates / Q000627:therapeutic use; D006526:Hepatitis C / Q000276:immunology*; D019698:Hepatitis C, Chronic / Q000188:drug therapy / Q000276:immunology*; D006801:Humans; D007093:Imidazoles / Q000627:therapeutic use; D007371:Interferon-gamma / Q000276:immunology; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology*; D012367:RNA, Viral / Q000276:immunology; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology*; D014779:Virus Replication / Q000187:drug effects / Q000276:immunology*; D000077211:Zoledronic Acid
D000941:Antigens; D050071:Bone Density Conservation Agents; D004164:Diphosphonates; D007093:Imidazoles; D012367:RNA, Viral; D016692:Receptors, Antigen, T-Cell, gamma-delta; D000077211:Zoledronic Acid; D007371:Interferon-gamma