RESEARCH ARTICLE
IFNγ Regulates Activated Vδ2+ T Cells through a Feedback Mechanism Mediated by Mesenchymal Stem Cells Karoline Fechter1, Akaitz Dorronsoro1, Emma Jakobsson1, Izaskun Ferrin1, Vale´rie Lang1, Pilar Sepulveda2, Daniel J. Pennington3, Ce´sar Trigueros1*
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OPEN ACCESS Citation: Fechter K, Dorronsoro A, Jakobsson E, Ferrin I, Lang V, Sepulveda P, et al. (2017) IFNγ Regulates Activated Vδ2+ T Cells through a Feedback Mechanism Mediated by Mesenchymal Stem Cells. PLoS ONE 12(1): e0169362. doi:10.1371/journal.pone.0169362 Editor: Joshua M. Hare, University of Miami School of Medicine, UNITED STATES Received: July 19, 2016 Accepted: December 15, 2016 Published: January 11, 2017 Copyright: © 2017 Fechter et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Data Availability Statement: All relevant data are within the paper and its Supporting Information files. Funding: This work was supported by the “Obra Social KUTXA”, Ministerio de Economı´a y Competitividad (FIS PI12/01982), the Basque Country Government and the Diputacio´n Foral de Guipu´zcoa. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
1 Fundacio´n Inbiomed, Foundation for Stem Cell Research, Mesenchymal Stem Cell Laboratory, Paseo Mikeletegi, San Sebastia´n, Spain, 2 Fundacio´n para la Investigacio´n Hospital Universitario La Fe, Valencia, Spain, 3 Blizard Institute, Barts and The London School of Medicine, Queen Mary University of London, London, United Kingdom * [email protected]
Abstract γδ T cells play a role in a wide range of diseases such as autoimmunity and cancer. The majority of circulating human γδ T lymphocytes express a Vγ9Vδ2+ (Vδ2+) T cell receptor (TCR) and following activation release pro-inflammatory cytokines. In this study, we show that IFNγ, produced by Vδ2+ cells, activates mesenchymal stem cell (MSC)-mediated immunosupression, which in turn exerts a negative feedback mechanism on γδ T cell function ranging from cytokine production to proliferation. Importantly, this modulatory effect is limited to a short period of time (
IFNγ Regulates Activated Vδ2+ T Cells through a Feedback Mechanism Mediated by Mesenchymal Stem Cells Karoline Fechter1, Akaitz Dorronsoro1, Emma Jakobsson1, Izaskun Ferrin1, Vale´rie Lang1, Pilar Sepulveda2, Daniel J. Pennington3, Ce´sar Trigueros1*
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OPEN ACCESS Citation: Fechter K, Dorronsoro A, Jakobsson E, Ferrin I, Lang V, Sepulveda P, et al. (2017) IFNγ Regulates Activated Vδ2+ T Cells through a Feedback Mechanism Mediated by Mesenchymal Stem Cells. PLoS ONE 12(1): e0169362. doi:10.1371/journal.pone.0169362 Editor: Joshua M. Hare, University of Miami School of Medicine, UNITED STATES Received: July 19, 2016 Accepted: December 15, 2016 Published: January 11, 2017 Copyright: © 2017 Fechter et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Data Availability Statement: All relevant data are within the paper and its Supporting Information files. Funding: This work was supported by the “Obra Social KUTXA”, Ministerio de Economı´a y Competitividad (FIS PI12/01982), the Basque Country Government and the Diputacio´n Foral de Guipu´zcoa. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
1 Fundacio´n Inbiomed, Foundation for Stem Cell Research, Mesenchymal Stem Cell Laboratory, Paseo Mikeletegi, San Sebastia´n, Spain, 2 Fundacio´n para la Investigacio´n Hospital Universitario La Fe, Valencia, Spain, 3 Blizard Institute, Barts and The London School of Medicine, Queen Mary University of London, London, United Kingdom * [email protected]
Abstract γδ T cells play a role in a wide range of diseases such as autoimmunity and cancer. The majority of circulating human γδ T lymphocytes express a Vγ9Vδ2+ (Vδ2+) T cell receptor (TCR) and following activation release pro-inflammatory cytokines. In this study, we show that IFNγ, produced by Vδ2+ cells, activates mesenchymal stem cell (MSC)-mediated immunosupression, which in turn exerts a negative feedback mechanism on γδ T cell function ranging from cytokine production to proliferation. Importantly, this modulatory effect is limited to a short period of time (
