Up-and-down immunity of pregnancy in humans.

Armand Bensussan,Philippe Le Bouteiller

doi:10.12688/f1000research.11690.1

Armand Bensussan, Philippe Le Bouteiller

Open Access

https://doi.org/10.12688/f1000research.11690.1

Copy DOI

Abstract

One part of the human placenta in early pregnancy is particularly important for local immunity: the decidua basalis, which is transformed endometrium located at the site of embryo implantation . This placental bed tissue contains both maternal uterine immune cells, including decidual natural killer (NK) cells, the dominant leukocyte population exhibiting a unique phenotype, and fetal extravillous trophoblast which comes into direct contact with maternal decidual cells . To establish a successful placental development and healthy pregnancy outcome, the maternal immune system must tolerate paternal antigens expressed by trophoblast cells yet remain efficient for clearing any local pathogen infection. This review deals mainly with decidual NK cells. A key element, among others, to achieve such dual functions is the direct interaction between activating and inhibitory receptors expressed by decidual NK cells and their specific ligands presented by trophoblast or other decidual cells. Depending whether maternal decidual cells and trophoblast are infected by viruses, the balance between activating and inhibitory receptor signals mediated by decidual NK cell–trophoblast cross-talk results in tolerance (healthy pregnancy) or specific killing (pathogen-infected cells).

Highlights

The human placenta consists of two components—a fetal and a maternal one—that must interact successfully for a healthy pregnancy outcome[1]
extravillous cytotrophoblast (EVCT) comes into close contact with various maternal immune cells: prominent granulated decidual natural killer cells, macrophages, CD4+ T cells, including T helper 17 (Th17) cells[8], and CD8+ T cells[4]
Decidual natural killer cells in healthy pregnancy: lack of cytotoxic function decidual natural killer (dNK) cells constitute the great majority of maternal immune cells present in early decidua basalis, where the EVCT infiltrates into maternal tissue

Summary

Introduction

The human placenta consists of two components—a fetal and a maternal one—that must interact successfully for a healthy pregnancy outcome[1]. We reported that the engagement of CD94/NKG2A inhibitory receptor with its specific ligand HLA-E expressed by EVCT is a dominant negative regulatory mechanism that prevents cytotoxicity toward trophoblast[37]. Another article indicated that isolated dNK cells expressing KIR2DS1 activating receptor acquired higher cytotoxic function than KIR2DS1negative dNK cells when in contact with HCMV-infected decidual stromal cells[13]. HLA-C expressed by EVCT is a specific ligand for various activating KIR dNK receptors[24] Such interactions result in the stimulation of dNK cell cytotoxic function[15]. DNK cells present in large numbers in decidua basalis play different roles at the beginning of pregnancy by interacting with specific EVCT-bound ligands, including HLA class I. Grant information The author(s) declared that no grants were involved in supporting this work

14. Le Bouteiller P

17. Le Bouteiller P

Findings

29. Le Bouteiller P