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Exosomes Derived From T Regulatory Cells Suppress CD8(+) Cytotoxic T Lymphocyte Proliferation and Prolong Liver Allograft Survival

BACKGROUND: CD8(+) cytotoxic T lymphocytes (CTLs) have been proved to exert crucial roles in immunological rejection. Exosomes (EXOs) secreted by CD4(+)CD25(+) regulatory T (Treg) cells is believed to be deeply involved in immune regulation. Nevertheless, whether immunomodulatory effect of CD4(+)CD2...

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Autores principales: Chen, Liang, Huang, Hanfei, Zhang, Weixin, Ding, Feifan, Fan, Zhenlei, Zeng, Zhong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: International Scientific Literature, Inc. 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6618337/
https://www.ncbi.nlm.nih.gov/pubmed/31258152
http://dx.doi.org/10.12659/MSM.917058
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author Chen, Liang
Huang, Hanfei
Zhang, Weixin
Ding, Feifan
Fan, Zhenlei
Zeng, Zhong
author_facet Chen, Liang
Huang, Hanfei
Zhang, Weixin
Ding, Feifan
Fan, Zhenlei
Zeng, Zhong
author_sort Chen, Liang
collection PubMed
description BACKGROUND: CD8(+) cytotoxic T lymphocytes (CTLs) have been proved to exert crucial roles in immunological rejection. Exosomes (EXOs) secreted by CD4(+)CD25(+) regulatory T (Treg) cells is believed to be deeply involved in immune regulation. Nevertheless, whether immunomodulatory effect of CD4(+)CD25(+) Treg cells on CD8(+) CTL depends on EXOs remains unknown and needs to be explored. MATERIAL/METHODS: We purified CD4(+)CD25(+) Treg cells followed by in vitro amplification. EXOs in culture supernatants of Treg cells was separated and identified. The effect of CD4(+)CD25(+) Treg cells and CD4(+)CD25(+) Treg cells-derived EXOs on CD8(+) CTL viability, proliferation, cell cycle mRNA, intracellular cytokines, and protein expression were investigated. RESULTS: We successfully obtained EXOs from CD4(+)CD25(+) Treg cells. The inhibition effect of EXOs on CD8(+) CTL was concentration-dependent. In addition, the inhibition effect of CD4(+)CD25(+) Treg cells could be reversed by GW4869, an EXOs inhibitor. The inhibition effect was associated with the regulation of IFN-γ and perforin. Our in vivo experiments proved that natural CD4(+)CD25(+) Treg cells-released EXOs can prolong liver allograft survival. CONCLUSIONS: CD4(+)CD25(+) Treg cells-derived EXOs could become an alternative tool for manipulating the immune system to discover novel underlying immunomodulatory mechanisms.
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spelling pubmed-66183372019-07-29 Exosomes Derived From T Regulatory Cells Suppress CD8(+) Cytotoxic T Lymphocyte Proliferation and Prolong Liver Allograft Survival Chen, Liang Huang, Hanfei Zhang, Weixin Ding, Feifan Fan, Zhenlei Zeng, Zhong Med Sci Monit Animal Study BACKGROUND: CD8(+) cytotoxic T lymphocytes (CTLs) have been proved to exert crucial roles in immunological rejection. Exosomes (EXOs) secreted by CD4(+)CD25(+) regulatory T (Treg) cells is believed to be deeply involved in immune regulation. Nevertheless, whether immunomodulatory effect of CD4(+)CD25(+) Treg cells on CD8(+) CTL depends on EXOs remains unknown and needs to be explored. MATERIAL/METHODS: We purified CD4(+)CD25(+) Treg cells followed by in vitro amplification. EXOs in culture supernatants of Treg cells was separated and identified. The effect of CD4(+)CD25(+) Treg cells and CD4(+)CD25(+) Treg cells-derived EXOs on CD8(+) CTL viability, proliferation, cell cycle mRNA, intracellular cytokines, and protein expression were investigated. RESULTS: We successfully obtained EXOs from CD4(+)CD25(+) Treg cells. The inhibition effect of EXOs on CD8(+) CTL was concentration-dependent. In addition, the inhibition effect of CD4(+)CD25(+) Treg cells could be reversed by GW4869, an EXOs inhibitor. The inhibition effect was associated with the regulation of IFN-γ and perforin. Our in vivo experiments proved that natural CD4(+)CD25(+) Treg cells-released EXOs can prolong liver allograft survival. CONCLUSIONS: CD4(+)CD25(+) Treg cells-derived EXOs could become an alternative tool for manipulating the immune system to discover novel underlying immunomodulatory mechanisms. International Scientific Literature, Inc. 2019-07-01 /pmc/articles/PMC6618337/ /pubmed/31258152 http://dx.doi.org/10.12659/MSM.917058 Text en © Med Sci Monit, 2019 This work is licensed under Creative Common Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0 (https://creativecommons.org/licenses/by-nc-nd/4.0/) )
spellingShingle Animal Study
Chen, Liang
Huang, Hanfei
Zhang, Weixin
Ding, Feifan
Fan, Zhenlei
Zeng, Zhong
Exosomes Derived From T Regulatory Cells Suppress CD8(+) Cytotoxic T Lymphocyte Proliferation and Prolong Liver Allograft Survival
title Exosomes Derived From T Regulatory Cells Suppress CD8(+) Cytotoxic T Lymphocyte Proliferation and Prolong Liver Allograft Survival
title_full Exosomes Derived From T Regulatory Cells Suppress CD8(+) Cytotoxic T Lymphocyte Proliferation and Prolong Liver Allograft Survival
title_fullStr Exosomes Derived From T Regulatory Cells Suppress CD8(+) Cytotoxic T Lymphocyte Proliferation and Prolong Liver Allograft Survival
title_full_unstemmed Exosomes Derived From T Regulatory Cells Suppress CD8(+) Cytotoxic T Lymphocyte Proliferation and Prolong Liver Allograft Survival
title_short Exosomes Derived From T Regulatory Cells Suppress CD8(+) Cytotoxic T Lymphocyte Proliferation and Prolong Liver Allograft Survival
title_sort exosomes derived from t regulatory cells suppress cd8(+) cytotoxic t lymphocyte proliferation and prolong liver allograft survival
topic Animal Study
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6618337/
https://www.ncbi.nlm.nih.gov/pubmed/31258152
http://dx.doi.org/10.12659/MSM.917058
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