Academic Journal

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

التفاصيل البيبلوغرافية
العنوان: Decidual CD8+T cells exhibit both residency and tolerance signatures modulated by decidual stromal cells
المؤلفون: Lu Liu, Xixi Huang, Chunfang Xu, Chunqin Chen, Weijie Zhao, Dajin Li, Liping Li, Li Wang, Meirong Du
المصدر: Journal of Translational Medicine, Vol 18, Iss 1, Pp 1-14 (2020)
بيانات النشر: BMC, 2020.
سنة النشر: 2020
المجموعة: LCC:Medicine
مصطلحات موضوعية: Maternal–fetal tolerance, CD8+T cell, Tissue resident memory cell, T cell exhaustion, Medicine
الوصف: Abstract 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 (TEM) and terminally differentiated effector memory cells (TEMRA). Both TEM and TEMRA 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.
نوع الوثيقة: article
وصف الملف: electronic resource
اللغة: English
تدمد: 1479-5876
Relation: http://link.springer.com/article/10.1186/s12967-020-02371-3; https://doaj.org/toc/1479-5876
DOI: 10.1186/s12967-020-02371-3
URL الوصول: https://doaj.org/article/2413616906cd4509adf26270d24a72d8
رقم الانضمام: edsdoj.2413616906cd4509adf26270d24a72d8
قاعدة البيانات: Directory of Open Access Journals
الوصف
تدمد:14795876
DOI:10.1186/s12967-020-02371-3