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Vδ2 T-Cells Kill ZIKV-Infected Cells by NKG2D-Mediated Cytotoxicity

An expansion of effector/activated Vδ2 T-cells was recently described in acute Zika virus (ZIKV)-infected patients, but their role in the protective immune response was not clarified. The aim of this study was to define the antiviral activity of Vδ2 T-cells against ZIKV-infected cells. The Vδ2 T-cel...

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Autores principales: Cimini, Eleonora, Sacchi, Alessandra, De Minicis, Sara, Bordoni, Veronica, Casetti, Rita, Grassi, Germana, Colavita, Francesca, Castilletti, Concetta, Capobianchi, Maria Rosaria, Ippolito, Giuseppe, Desimio, Maria Giovanna, Doria, Margherita, Agrati, Chiara
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6781265/
https://www.ncbi.nlm.nih.gov/pubmed/31547470
http://dx.doi.org/10.3390/microorganisms7090350
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author Cimini, Eleonora
Sacchi, Alessandra
De Minicis, Sara
Bordoni, Veronica
Casetti, Rita
Grassi, Germana
Colavita, Francesca
Castilletti, Concetta
Capobianchi, Maria Rosaria
Ippolito, Giuseppe
Desimio, Maria Giovanna
Doria, Margherita
Agrati, Chiara
author_facet Cimini, Eleonora
Sacchi, Alessandra
De Minicis, Sara
Bordoni, Veronica
Casetti, Rita
Grassi, Germana
Colavita, Francesca
Castilletti, Concetta
Capobianchi, Maria Rosaria
Ippolito, Giuseppe
Desimio, Maria Giovanna
Doria, Margherita
Agrati, Chiara
author_sort Cimini, Eleonora
collection PubMed
description An expansion of effector/activated Vδ2 T-cells was recently described in acute Zika virus (ZIKV)-infected patients, but their role in the protective immune response was not clarified. The aim of this study was to define the antiviral activity of Vδ2 T-cells against ZIKV-infected cells. The Vδ2 T-cells expansion and their cytotoxic activity against ZIKV-infected cells were tested in vitro and analyzed by RT-PCR and flow cytometry. We found that ZIKV infection was able to induce Vδ2 T-cells expansion and sensitized A549 cells to Vδ2-mediated killing. Indeed, expanded Vδ2 T-cells killed ZIKV-infected cells through degranulation and perforin release. Moreover, ZIKV infection was able to increase the expression on A549 cells of NKG2D ligands (NKG2DLs), namely MICA, MICB, and ULBP2, at both the mRNA and protein levels, suggesting the possible involvement of these molecules in the recognition by NKG2D-expressing Vδ2 T-cells. Indeed, the killing of ZIKV-infected cells by expanded Vδ2 T-cells was mediated by NKG2D/NKG2DL interaction as NKG2D neutralization abrogated Vδ2 cytotoxicity. Our data showed a strong antiviral activity of Vδ2 T-cells against ZIKV-infected cells, suggesting their involvement in the protective immune response. Other studies are necessary to investigate whether the lack of Vδ2 T-cells expansion in vivo may be associated with disease complications.
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spelling pubmed-67812652019-10-30 Vδ2 T-Cells Kill ZIKV-Infected Cells by NKG2D-Mediated Cytotoxicity Cimini, Eleonora Sacchi, Alessandra De Minicis, Sara Bordoni, Veronica Casetti, Rita Grassi, Germana Colavita, Francesca Castilletti, Concetta Capobianchi, Maria Rosaria Ippolito, Giuseppe Desimio, Maria Giovanna Doria, Margherita Agrati, Chiara Microorganisms Article An expansion of effector/activated Vδ2 T-cells was recently described in acute Zika virus (ZIKV)-infected patients, but their role in the protective immune response was not clarified. The aim of this study was to define the antiviral activity of Vδ2 T-cells against ZIKV-infected cells. The Vδ2 T-cells expansion and their cytotoxic activity against ZIKV-infected cells were tested in vitro and analyzed by RT-PCR and flow cytometry. We found that ZIKV infection was able to induce Vδ2 T-cells expansion and sensitized A549 cells to Vδ2-mediated killing. Indeed, expanded Vδ2 T-cells killed ZIKV-infected cells through degranulation and perforin release. Moreover, ZIKV infection was able to increase the expression on A549 cells of NKG2D ligands (NKG2DLs), namely MICA, MICB, and ULBP2, at both the mRNA and protein levels, suggesting the possible involvement of these molecules in the recognition by NKG2D-expressing Vδ2 T-cells. Indeed, the killing of ZIKV-infected cells by expanded Vδ2 T-cells was mediated by NKG2D/NKG2DL interaction as NKG2D neutralization abrogated Vδ2 cytotoxicity. Our data showed a strong antiviral activity of Vδ2 T-cells against ZIKV-infected cells, suggesting their involvement in the protective immune response. Other studies are necessary to investigate whether the lack of Vδ2 T-cells expansion in vivo may be associated with disease complications. MDPI 2019-09-12 /pmc/articles/PMC6781265/ /pubmed/31547470 http://dx.doi.org/10.3390/microorganisms7090350 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Cimini, Eleonora
Sacchi, Alessandra
De Minicis, Sara
Bordoni, Veronica
Casetti, Rita
Grassi, Germana
Colavita, Francesca
Castilletti, Concetta
Capobianchi, Maria Rosaria
Ippolito, Giuseppe
Desimio, Maria Giovanna
Doria, Margherita
Agrati, Chiara
Vδ2 T-Cells Kill ZIKV-Infected Cells by NKG2D-Mediated Cytotoxicity
title Vδ2 T-Cells Kill ZIKV-Infected Cells by NKG2D-Mediated Cytotoxicity
title_full Vδ2 T-Cells Kill ZIKV-Infected Cells by NKG2D-Mediated Cytotoxicity
title_fullStr Vδ2 T-Cells Kill ZIKV-Infected Cells by NKG2D-Mediated Cytotoxicity
title_full_unstemmed Vδ2 T-Cells Kill ZIKV-Infected Cells by NKG2D-Mediated Cytotoxicity
title_short Vδ2 T-Cells Kill ZIKV-Infected Cells by NKG2D-Mediated Cytotoxicity
title_sort vδ2 t-cells kill zikv-infected cells by nkg2d-mediated cytotoxicity
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6781265/
https://www.ncbi.nlm.nih.gov/pubmed/31547470
http://dx.doi.org/10.3390/microorganisms7090350
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