title: Antiviral activity of human Vδ2 T-cells against WNV includes both cytolytic and non-cytolytic mechanisms.
abstract: West Nile virus (WNV) causes a severe central nervous system infection in humans, primarily in the elderly and immunocompromised subjects. Human γδ T-cells play a critical role in the immune response against viruses, and studies of WNV meningoencephalitis in laboratory mice described a role of γδ T-cells in the protective immune response. Aim of this study was to analyze the cytolytic and non-cytolytic antiviral activity of human Vδ2 T-cells against WNV replication. The anti-WNV activity of soluble factor released by zoledronic acid (ZA)-activated Vδ2 T-cell lines and the cytotoxic capability of Vδ2 T-cell lines against WNV-infected cells were tested in vitro. The activation of Vδ2 T-cell lines was able to inhibit WNV replication through the release of soluble factors. IFN-γ is massively released by activated Vδ2 T-cell lines and is involved in the anti-WNV activity. Moreover, the Vδ2 T-cell lines can efficiently kill WNV-infected cells possibly through perforin-mediated mechanism. Altogether, our results provide insight into the effector functions of human Vδ2 T-cells against WNV. The possibility to target these cells by ZA, a commercially available drug used in humans, could potentially offer a new immunotherapeutic strategy for WNV infection.
authors.affiliation: Cellular Immunology Laboratory.|Laboratory of Virology, "L. Spallanzani" National Institute for Infectious Diseases (INMI), Rome, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Agrati
authors.affiliation: Laboratory of Virology, "L. Spallanzani" National Institute for Infectious Diseases (INMI), Rome, Italy.
authors.forename: Concetta
authors.initials: C
authors.lastname: Castilletti
authors.affiliation: Cellular Immunology Laboratory.
authors.forename: Eleonora
authors.initials: E
authors.lastname: Cimini
authors.affiliation: Cellular Immunology Laboratory.
authors.forename: Antonella
authors.initials: A
authors.lastname: Romanelli
authors.affiliation: Laboratory of Virology, "L. Spallanzani" National Institute for Infectious Diseases (INMI), Rome, Italy.
authors.forename: Daniele
authors.initials: D
authors.lastname: Lapa
authors.affiliation: Laboratory of Virology, "L. Spallanzani" National Institute for Infectious Diseases (INMI), Rome, Italy.
authors.forename: Serena
authors.initials: S
authors.lastname: Quartu
authors.affiliation: Cellular Immunology Laboratory.
authors.forename: Federico
authors.initials: F
authors.lastname: Martini
authors.affiliation: Laboratory of Virology, "L. Spallanzani" National Institute for Infectious Diseases (INMI), Rome, Italy.
authors.forename: Maria Rosaria
authors.initials: MR
authors.lastname: Capobianchi
mesh_terms: D000818:Animals; D002460:Cell Line; D004164:Diphosphonates / Q000494:pharmacology; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D051379:Mice; D016176:T-Lymphocyte Subsets / Q000502:physiology*; D014901:West Nile Fever / Q000276:immunology* / Q000821:virology*; D014902:West Nile virus / Q000276:immunology*; D000077211:Zoledronic Acid
chemical_list: D004164:Diphosphonates; D007093:Imidazoles; D000077211:Zoledronic Acid
keywords: IFN-g; Innate immunity; cytotoxicity; gd T-cells