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Decidual CD8(+)T cells exhibit both residency and tolerance signatures modulated by decidual stromal cells

BACKGROUND: During early pregnancy, tolerance of the semi-allogeneic fetus necessitates comprehensive modifications of the maternal immune system. How decidual CD8(+)T (CD8(+)dT) cells balance maternal tolerance of the fetus with defense from invading pathogens remains undefined. METHODS: We investi...

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Autores principales: Liu, Lu, Huang, Xixi, Xu, Chunfang, Chen, Chunqin, Zhao, Weijie, Li, Dajin, Li, Liping, Wang, Li, Du, Meirong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7268777/
https://www.ncbi.nlm.nih.gov/pubmed/32487187
http://dx.doi.org/10.1186/s12967-020-02371-3
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author Liu, Lu
Huang, Xixi
Xu, Chunfang
Chen, Chunqin
Zhao, Weijie
Li, Dajin
Li, Liping
Wang, Li
Du, Meirong
author_facet Liu, Lu
Huang, Xixi
Xu, Chunfang
Chen, Chunqin
Zhao, Weijie
Li, Dajin
Li, Liping
Wang, Li
Du, Meirong
author_sort Liu, Lu
collection PubMed
description BACKGROUND: During early pregnancy, tolerance of the semi-allogeneic fetus necessitates comprehensive modifications of the maternal immune system. How decidual CD8(+)T (CD8(+)dT) cells balance maternal tolerance of the fetus with defense from invading pathogens remains undefined. METHODS: We investigated the distribution patterns of CD8(+)T cells and their heterogeneity in paired peripheral blood and decidual tissue in the first trimester of pregnancy using flow cytometry and mRNA-Seq. Gene Set Enrichment Analysis was utilized to determine the transcriptional features of CD8(+)dT cells. Moreover, we examined activation of T cells when they were cocultured with trophoblasts, in addition to the effect of the fetal–maternal environment on peripheral CD8(+)T (CD8(+)pT) cells. RESULTS: We found that, compared with CD8(+)pT cells, CD8(+)dT cells consisted mainly of effector memory cells (T(EM)) and terminally differentiated effector memory cells (T(EMRA)). Both T(EM) and T(EMRA) subsets contained increased numbers of CD27(+)CD28(−) cells, which have been shown to possess only partial effector functions. In-depth analysis of the gene-expression profiles of CD8(+)dT cells revealed significant enrichment in T cell exhaustion-related genes and core tissue residency signature genes that have been found recently to be shared by tissue resident memory cells and tumor(−)infiltrating lymphocytes (TILs). In accordance with gene expression, protein levels of the exhaustion-related molecules PD-1 and CD39 and the tissue resident molecules CD103 and CXCR3 were increased significantly with almost no perforin secretion in CD8(+)dT cells compared with CD8(+)pT cells. However, the levels of granzyme B, IFN-γ, and IL-4 in CD8(+)dT cells were increased significantly compared with those in CD8(+)pT cells. Both CD8(+)dT and CD8(+)pT cells were not activated after being cocultured with autologous trophoblast cells. Moreover, the production of granzyme B in CD103(+)CD8(+)dT cells decreased significantly compared with that in their CD103(−) counterparts. Coculture with decidual stromal cells and trophoblasts upregulated CD103 expression significantly in CD8(+)pT cells. CONCLUSIONS: Our findings indicate that the selective silencing of effector functions of resident CD8(+)dT cells may favor maternal–fetal tolerance and that the decidual microenvironment plays an important role in promoting the residency of CD8(+)T cells and their tolerance–defense balance.
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spelling pubmed-72687772020-06-08 Decidual CD8(+)T cells exhibit both residency and tolerance signatures modulated by decidual stromal cells Liu, Lu Huang, Xixi Xu, Chunfang Chen, Chunqin Zhao, Weijie Li, Dajin Li, Liping Wang, Li Du, Meirong J Transl Med Research BACKGROUND: During early pregnancy, tolerance of the semi-allogeneic fetus necessitates comprehensive modifications of the maternal immune system. How decidual CD8(+)T (CD8(+)dT) cells balance maternal tolerance of the fetus with defense from invading pathogens remains undefined. METHODS: We investigated the distribution patterns of CD8(+)T cells and their heterogeneity in paired peripheral blood and decidual tissue in the first trimester of pregnancy using flow cytometry and mRNA-Seq. Gene Set Enrichment Analysis was utilized to determine the transcriptional features of CD8(+)dT cells. Moreover, we examined activation of T cells when they were cocultured with trophoblasts, in addition to the effect of the fetal–maternal environment on peripheral CD8(+)T (CD8(+)pT) cells. RESULTS: We found that, compared with CD8(+)pT cells, CD8(+)dT cells consisted mainly of effector memory cells (T(EM)) and terminally differentiated effector memory cells (T(EMRA)). Both T(EM) and T(EMRA) subsets contained increased numbers of CD27(+)CD28(−) cells, which have been shown to possess only partial effector functions. In-depth analysis of the gene-expression profiles of CD8(+)dT cells revealed significant enrichment in T cell exhaustion-related genes and core tissue residency signature genes that have been found recently to be shared by tissue resident memory cells and tumor(−)infiltrating lymphocytes (TILs). In accordance with gene expression, protein levels of the exhaustion-related molecules PD-1 and CD39 and the tissue resident molecules CD103 and CXCR3 were increased significantly with almost no perforin secretion in CD8(+)dT cells compared with CD8(+)pT cells. However, the levels of granzyme B, IFN-γ, and IL-4 in CD8(+)dT cells were increased significantly compared with those in CD8(+)pT cells. Both CD8(+)dT and CD8(+)pT cells were not activated after being cocultured with autologous trophoblast cells. Moreover, the production of granzyme B in CD103(+)CD8(+)dT cells decreased significantly compared with that in their CD103(−) counterparts. Coculture with decidual stromal cells and trophoblasts upregulated CD103 expression significantly in CD8(+)pT cells. CONCLUSIONS: Our findings indicate that the selective silencing of effector functions of resident CD8(+)dT cells may favor maternal–fetal tolerance and that the decidual microenvironment plays an important role in promoting the residency of CD8(+)T cells and their tolerance–defense balance. BioMed Central 2020-06-01 /pmc/articles/PMC7268777/ /pubmed/32487187 http://dx.doi.org/10.1186/s12967-020-02371-3 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/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Liu, Lu
Huang, Xixi
Xu, Chunfang
Chen, Chunqin
Zhao, Weijie
Li, Dajin
Li, Liping
Wang, Li
Du, Meirong
Decidual CD8(+)T cells exhibit both residency and tolerance signatures modulated by decidual stromal cells
title Decidual CD8(+)T cells exhibit both residency and tolerance signatures modulated by decidual stromal cells
title_full Decidual CD8(+)T cells exhibit both residency and tolerance signatures modulated by decidual stromal cells
title_fullStr Decidual CD8(+)T cells exhibit both residency and tolerance signatures modulated by decidual stromal cells
title_full_unstemmed Decidual CD8(+)T cells exhibit both residency and tolerance signatures modulated by decidual stromal cells
title_short Decidual CD8(+)T cells exhibit both residency and tolerance signatures modulated by decidual stromal cells
title_sort decidual cd8(+)t cells exhibit both residency and tolerance signatures modulated by decidual stromal cells
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7268777/
https://www.ncbi.nlm.nih.gov/pubmed/32487187
http://dx.doi.org/10.1186/s12967-020-02371-3
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