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CD4(+)CD25(+)Foxp3(+) regulatory T cells suppress NKG2D-mediated NK cell cytotoxicity in peripheral blood
BACKGROUND: Studies have shown that CD4(+)CD25(+)Foxp3(+)Treg cells suppress NKG2D expression on NK cells via a cell contact-dependent mechanism and increased TGF-β and IL-10 production in some cancer models. We herein aimed to explore whether CD4(+)CD25(+)Foxp3(+)Tregs suppress NKG2D-mediated NK ce...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Wolters Kluwer Health
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6708973/ https://www.ncbi.nlm.nih.gov/pubmed/31145286 http://dx.doi.org/10.1097/MD.0000000000015722 |
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author | Geng, Xu Li, Ming Cui, Bin Lu, Chao Liu, Xiaowen Zhang, Peng Liu, Bin Ma, Chunyan Shen, Yajuan Lu, Zhiming |
author_facet | Geng, Xu Li, Ming Cui, Bin Lu, Chao Liu, Xiaowen Zhang, Peng Liu, Bin Ma, Chunyan Shen, Yajuan Lu, Zhiming |
author_sort | Geng, Xu |
collection | PubMed |
description | BACKGROUND: Studies have shown that CD4(+)CD25(+)Foxp3(+)Treg cells suppress NKG2D expression on NK cells via a cell contact-dependent mechanism and increased TGF-β and IL-10 production in some cancer models. We herein aimed to explore whether CD4(+)CD25(+)Foxp3(+)Tregs suppress NKG2D-mediated NK cell cytotoxicity in peripheral blood and elucidate the exact mechanism underlying this phenomenon. METHODS: To explore the function of NKG2D, NK cell cultures were treated with an NKG2D-blocking antibody to block these receptors. Additionally, TGF-β- and IL-10-blocking antibodies were added to NK and CD4(+)CD25(+)Foxp3(+)Treg cell cocultures to evaluate whether the latter cells suppress NKG2D expression of NK cells via increasing the production of TGF-β and IL-10. The expression of NKG2D on NK cells was detected by 3-color flow cytometry, and NK cell activity was assessed by 3 assays: a nonradioactive cytotoxicity assay, an ELISA measuring IFN-γ production and a flow cytometry assay to evaluate CD107a expression. RESULTS: Blocking NKG2D decreased NK cell cytotoxicity, IFN-γ production and CD107a expression. Moreover, blocking TGF-β and IL-10 substantially increased the NKG2D expression in NK and CD4(+)CD25(+)Foxp3(+)Treg cell cocultures. Similarly, blocking TGF-β and IL-10 enhanced NK cell cytotoxicity, IFN-γ production and CD107a expression; Transwell insert assays also revealed increased IFN-γ production and CD107a and NKG2D expression. CONCLUSION: CD4(+)CD25(+)Foxp3(+)Tregs suppress NKG2D-mediated NK cell cytotoxicity in peripheral blood via a cell contact-dependent mechanism and increased TGF-β and IL-10 production. |
format | Online Article Text |
id | pubmed-6708973 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Wolters Kluwer Health |
record_format | MEDLINE/PubMed |
spelling | pubmed-67089732019-10-01 CD4(+)CD25(+)Foxp3(+) regulatory T cells suppress NKG2D-mediated NK cell cytotoxicity in peripheral blood Geng, Xu Li, Ming Cui, Bin Lu, Chao Liu, Xiaowen Zhang, Peng Liu, Bin Ma, Chunyan Shen, Yajuan Lu, Zhiming Medicine (Baltimore) Research Article BACKGROUND: Studies have shown that CD4(+)CD25(+)Foxp3(+)Treg cells suppress NKG2D expression on NK cells via a cell contact-dependent mechanism and increased TGF-β and IL-10 production in some cancer models. We herein aimed to explore whether CD4(+)CD25(+)Foxp3(+)Tregs suppress NKG2D-mediated NK cell cytotoxicity in peripheral blood and elucidate the exact mechanism underlying this phenomenon. METHODS: To explore the function of NKG2D, NK cell cultures were treated with an NKG2D-blocking antibody to block these receptors. Additionally, TGF-β- and IL-10-blocking antibodies were added to NK and CD4(+)CD25(+)Foxp3(+)Treg cell cocultures to evaluate whether the latter cells suppress NKG2D expression of NK cells via increasing the production of TGF-β and IL-10. The expression of NKG2D on NK cells was detected by 3-color flow cytometry, and NK cell activity was assessed by 3 assays: a nonradioactive cytotoxicity assay, an ELISA measuring IFN-γ production and a flow cytometry assay to evaluate CD107a expression. RESULTS: Blocking NKG2D decreased NK cell cytotoxicity, IFN-γ production and CD107a expression. Moreover, blocking TGF-β and IL-10 substantially increased the NKG2D expression in NK and CD4(+)CD25(+)Foxp3(+)Treg cell cocultures. Similarly, blocking TGF-β and IL-10 enhanced NK cell cytotoxicity, IFN-γ production and CD107a expression; Transwell insert assays also revealed increased IFN-γ production and CD107a and NKG2D expression. CONCLUSION: CD4(+)CD25(+)Foxp3(+)Tregs suppress NKG2D-mediated NK cell cytotoxicity in peripheral blood via a cell contact-dependent mechanism and increased TGF-β and IL-10 production. Wolters Kluwer Health 2019-05-31 /pmc/articles/PMC6708973/ /pubmed/31145286 http://dx.doi.org/10.1097/MD.0000000000015722 Text en Copyright © 2019 the Author(s). Published by Wolters Kluwer Health, Inc. http://creativecommons.org/licenses/by-nc-nd/4.0 This is an open access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. http://creativecommons.org/licenses/by-nc-nd/4.0 |
spellingShingle | Research Article Geng, Xu Li, Ming Cui, Bin Lu, Chao Liu, Xiaowen Zhang, Peng Liu, Bin Ma, Chunyan Shen, Yajuan Lu, Zhiming CD4(+)CD25(+)Foxp3(+) regulatory T cells suppress NKG2D-mediated NK cell cytotoxicity in peripheral blood |
title | CD4(+)CD25(+)Foxp3(+) regulatory T cells suppress NKG2D-mediated NK cell cytotoxicity in peripheral blood |
title_full | CD4(+)CD25(+)Foxp3(+) regulatory T cells suppress NKG2D-mediated NK cell cytotoxicity in peripheral blood |
title_fullStr | CD4(+)CD25(+)Foxp3(+) regulatory T cells suppress NKG2D-mediated NK cell cytotoxicity in peripheral blood |
title_full_unstemmed | CD4(+)CD25(+)Foxp3(+) regulatory T cells suppress NKG2D-mediated NK cell cytotoxicity in peripheral blood |
title_short | CD4(+)CD25(+)Foxp3(+) regulatory T cells suppress NKG2D-mediated NK cell cytotoxicity in peripheral blood |
title_sort | cd4(+)cd25(+)foxp3(+) regulatory t cells suppress nkg2d-mediated nk cell cytotoxicity in peripheral blood |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6708973/ https://www.ncbi.nlm.nih.gov/pubmed/31145286 http://dx.doi.org/10.1097/MD.0000000000015722 |
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