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


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-?, 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.

SUBMITTER: Liu L 

PROVIDER: S-EPMC7268777 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature

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Decidual CD8<sup>+</sup>T cells exhibit both residency and tolerance signatures modulated by decidual stromal cells.

Liu Lu L   Huang Xixi X   Xu Chunfang C   Chen Chunqin C   Zhao Weijie W   Li Dajin D   Li Liping L   Wang Li L   Du Meirong M  

Journal of translational medicine 20200601 1


<h4>Background</h4>During early pregnancy, tolerance of the semi-allogeneic fetus necessitates comprehensive modifications of the maternal immune system. How decidual CD8<sup>+</sup>T (CD8<sup>+</sup>dT) cells balance maternal tolerance of the fetus with defense from invading pathogens remains undefined.<h4>Methods</h4>We investigated the distribution patterns of CD8<sup>+</sup>T cells and their heterogeneity in paired peripheral blood and decidual tissue in the first trimester of pregnancy usin  ...[more]

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