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Decidual T Cells Exhibit a Highly Differentiated Phenotype and Demonstrate Potential Fetal Specificity and a Strong Transcriptional Response to IFN.

ABSTRACT: Immune tolerance during human pregnancy is maintained by a range of modifications to the local and systemic maternal immune system. Lymphoid infiltration is seen at the implantation site of the fetal-maternal interface, and decidual NK cells have been demonstrated to facilitate extravillous trophoblast invasion into maternal decidua during the first trimester, optimizing hemochorial placentation. However, although there is considerable T cell infiltration of the maternal decidua, the functional properties of this T cell response remain poorly defined. We investigated the specificity and regulation of CD4+ and CD8+ T cells obtained from human third trimester decidua and demonstrated that decidual CD4+ and CD8+ T cells exhibit a highly differentiated effector memory phenotype in comparison with peripheral blood and display increased production of IFN-? and IL-4. Moreover, decidual T cells proliferated in response to fetal tissue, and depletion of T regulatory cells led to an increase in fetal-specific proliferation. HY-specific T cells were detectable in the decidua of women with male pregnancies and were shown to be highly differentiated. Transcriptional analysis of decidual T cells revealed a unique gene profile characterized by elevated expression of proteins associated with the response to IFN signaling. These data have considerable importance both for the study of healthy placentation and for the investigation of the potential importance of fetal-specific alloreactive immune responses within disorders of pregnancy.

SUBMITTER: Powell RM

PROVIDER: S-EPMC5679367 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature

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Decidual T Cells Exhibit a Highly Differentiated Phenotype and Demonstrate Potential Fetal Specificity and a Strong Transcriptional Response to IFN.

Powell Richard M RM Lissauer David D Tamblyn Jennifer J Beggs Andrew A Cox Philip P Moss Paul P Kilby Mark D MD

Journal of immunology (Baltimore, Md. : 1950) 20171006 10

Immune tolerance during human pregnancy is maintained by a range of modifications to the local and systemic maternal immune system. Lymphoid infiltration is seen at the implantation site of the fetal-maternal interface, and decidual NK cells have been demonstrated to facilitate extravillous trophoblast invasion into maternal decidua during the first trimester, optimizing hemochorial placentation. However, although there is considerable T cell infiltration of the maternal decidua, the functional ...[more]

PMID: 28986438

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Project description:BackgroundDuring 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.MethodsWe 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.ResultsWe 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.ConclusionsOur 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.

Dataset Information

Decidual T Cells Exhibit a Highly Differentiated Phenotype and Demonstrate Potential Fetal Specificity and a Strong Transcriptional Response to IFN.

Publications

Decidual T Cells Exhibit a Highly Differentiated Phenotype and Demonstrate Potential Fetal Specificity and a Strong Transcriptional Response to IFN.

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