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Suppressive activity of Vδ2(+) γδ T cells on αβ T cells is licensed by TCR signaling and correlates with signal strength
Despite recent progress in the understanding of γδ T cells’ roles and functions, their interaction with αβ T cells still remains to be elucidated. In this study, we sought to clarify what precisely endows peripheral Vδ2(+) T cells with immunosuppressive function on autologous αβ T cells. We found th...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Springer Berlin Heidelberg
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7113223/ https://www.ncbi.nlm.nih.gov/pubmed/31982940 http://dx.doi.org/10.1007/s00262-019-02469-8 |
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author | Schilbach, Karin Krickeberg, Naomi Kaißer, Carlotta Mingram, Simon Kind, Janika Siegers, Gabrielle M. Hashimoto, Hisayoshi |
author_facet | Schilbach, Karin Krickeberg, Naomi Kaißer, Carlotta Mingram, Simon Kind, Janika Siegers, Gabrielle M. Hashimoto, Hisayoshi |
author_sort | Schilbach, Karin |
collection | PubMed |
description | Despite recent progress in the understanding of γδ T cells’ roles and functions, their interaction with αβ T cells still remains to be elucidated. In this study, we sought to clarify what precisely endows peripheral Vδ2(+) T cells with immunosuppressive function on autologous αβ T cells. We found that negatively freshly isolated Vδ2(+) T cells do not exhibit suppressive behavior, even after stimulation with IL-12/IL-18/IL-15 or the sheer contact with butyrophilin-3A1-expressing tumor cell lines (U251 or SK-Mel-28). On the other hand, Vδ2(+) T cells positively isolated through TCR crosslinking or after prolonged stimulation with isopentenyl pyrophosphate (IPP) mediate strong inhibitory effects on αβ T cell proliferation. Stimulation with IPP in the presence of IL-15 induces the most robust suppressive phenotype of Vδ2(+) T cells. This indicates that Vδ2(+) T cells’ suppressive activity is dependent on a TCR signal and that the degree of suppression correlates with its strength. Vδ2(+) T cell immunosuppression does not correlate with their Foxp3 expression but rather with their PD-L1 protein expression, evidenced by the massive reduction of suppressive activity when using a blocking antibody. In conclusion, pharmacologic stimulation of Vδ2(+) T cells via the Vδ2 TCR for activation and expansion induces Vδ2(+) T cells' potent killer activity while simultaneously licensing them to suppress αβ T cell responses. Taken together, the study is a further step to understand—in more detail—the suppressive activity of Vδ2(+) γδ T cells. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00262-019-02469-8) contains supplementary material, which is available to authorized users. |
format | Online Article Text |
id | pubmed-7113223 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Springer Berlin Heidelberg |
record_format | MEDLINE/PubMed |
spelling | pubmed-71132232020-04-06 Suppressive activity of Vδ2(+) γδ T cells on αβ T cells is licensed by TCR signaling and correlates with signal strength Schilbach, Karin Krickeberg, Naomi Kaißer, Carlotta Mingram, Simon Kind, Janika Siegers, Gabrielle M. Hashimoto, Hisayoshi Cancer Immunol Immunother Original Article Despite recent progress in the understanding of γδ T cells’ roles and functions, their interaction with αβ T cells still remains to be elucidated. In this study, we sought to clarify what precisely endows peripheral Vδ2(+) T cells with immunosuppressive function on autologous αβ T cells. We found that negatively freshly isolated Vδ2(+) T cells do not exhibit suppressive behavior, even after stimulation with IL-12/IL-18/IL-15 or the sheer contact with butyrophilin-3A1-expressing tumor cell lines (U251 or SK-Mel-28). On the other hand, Vδ2(+) T cells positively isolated through TCR crosslinking or after prolonged stimulation with isopentenyl pyrophosphate (IPP) mediate strong inhibitory effects on αβ T cell proliferation. Stimulation with IPP in the presence of IL-15 induces the most robust suppressive phenotype of Vδ2(+) T cells. This indicates that Vδ2(+) T cells’ suppressive activity is dependent on a TCR signal and that the degree of suppression correlates with its strength. Vδ2(+) T cell immunosuppression does not correlate with their Foxp3 expression but rather with their PD-L1 protein expression, evidenced by the massive reduction of suppressive activity when using a blocking antibody. In conclusion, pharmacologic stimulation of Vδ2(+) T cells via the Vδ2 TCR for activation and expansion induces Vδ2(+) T cells' potent killer activity while simultaneously licensing them to suppress αβ T cell responses. Taken together, the study is a further step to understand—in more detail—the suppressive activity of Vδ2(+) γδ T cells. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00262-019-02469-8) contains supplementary material, which is available to authorized users. Springer Berlin Heidelberg 2020-01-25 2020 /pmc/articles/PMC7113223/ /pubmed/31982940 http://dx.doi.org/10.1007/s00262-019-02469-8 Text en © The Author(s) 2020 Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Original Article Schilbach, Karin Krickeberg, Naomi Kaißer, Carlotta Mingram, Simon Kind, Janika Siegers, Gabrielle M. Hashimoto, Hisayoshi Suppressive activity of Vδ2(+) γδ T cells on αβ T cells is licensed by TCR signaling and correlates with signal strength |
title | Suppressive activity of Vδ2(+) γδ T cells on αβ T cells is licensed by TCR signaling and correlates with signal strength |
title_full | Suppressive activity of Vδ2(+) γδ T cells on αβ T cells is licensed by TCR signaling and correlates with signal strength |
title_fullStr | Suppressive activity of Vδ2(+) γδ T cells on αβ T cells is licensed by TCR signaling and correlates with signal strength |
title_full_unstemmed | Suppressive activity of Vδ2(+) γδ T cells on αβ T cells is licensed by TCR signaling and correlates with signal strength |
title_short | Suppressive activity of Vδ2(+) γδ T cells on αβ T cells is licensed by TCR signaling and correlates with signal strength |
title_sort | suppressive activity of vδ2(+) γδ t cells on αβ t cells is licensed by tcr signaling and correlates with signal strength |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7113223/ https://www.ncbi.nlm.nih.gov/pubmed/31982940 http://dx.doi.org/10.1007/s00262-019-02469-8 |
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