TY - JOUR
T1 - Antiviral activity of human Vδ2 T-cells against WNV includes both cytolytic and non-cytolytic mechanisms
AU - Agrati, Chiara
AU - Castilletti, Concetta
AU - Cimini, Eleonora
AU - Romanelli, Antonella
AU - Lapa, Daniele
AU - Quartu, Serena
AU - Martini, Federico
AU - Capobianchi, Maria Rosaria
PY - 2016/4/1
Y1 - 2016/4/1
N2 - West Nile virus (WNV) causes a severe central nervous system infection in humans, primarily in the elderly and immunocompromised subjects. Human γδT-cells play a critical role in the immune response against viruses, and studies of WNV meningoencephalitis in laboratory mice described a role of γδT-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.
AB - West Nile virus (WNV) causes a severe central nervous system infection in humans, primarily in the elderly and immunocompromised subjects. Human γδT-cells play a critical role in the immune response against viruses, and studies of WNV meningoencephalitis in laboratory mice described a role of γδT-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.
KW - Cytotoxicity
KW - IFN-γ
KW - Innate immunity
KW - γδ T-cells
UR - http://www.scopus.com/inward/record.url?scp=84971378760&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84971378760&partnerID=8YFLogxK
M3 - Article
C2 - 27196553
AN - SCOPUS:84971378760
VL - 39
SP - 139
EP - 142
JO - New Microbiologica
JF - New Microbiologica
SN - 1121-7138
IS - 2
ER -