Decidual γδT cells of early human pregnancy produce angiogenic and immunomodulatory proteins while also possessing cytotoxic potential.

During pregnancy, the maternal immune system must allow and support the growth of the developing placenta while maintaining the integrity of the mother's body. The trophoblast's unique HLA signature is a key factor in this physiological process. This study focuses on decidual γδT cell populations and examines their expression of receptors that bind to non-classical HLA molecules, HLA-E and HLA-G.

The Role of Hydrogen-Peroxide (HO) Produced by Vaginal Microbiota in Female Reproductive Health.

Female reproductive health is strongly associated with healthy vaginal microbiota, which is thought to be ensured by the dominance of certain species. Lactobacilli control the vaginal microenvironment through several factors and mechanisms. One of them is their ability to produce hydrogen peroxide (HO).

Corrigendum: Gamma/Delta T Cells in the Course of Healthy Human Pregnancy: Cytotoxic Potential and the Tendency of CD8 Expression Make CD56+ γδT Cells a Unique Lymphocyte Subset.

[This corrects the article DOI: 10.3389/fimmu.2020.

The Role of Type I and Type II NKT Cells in Materno-Fetal Immunity.

NKT cells represent a small but significant immune cell population as being a part of and bridging innate and adaptive immunity. Their ability to exert strong immune responses via cytotoxicity and cytokine secretion makes them significant immune effectors. Since pregnancy requires unconventional maternal immunity with a tolerogenic phenotype, investigation of the possible role of NKT cells in materno-fetal immune tolerance mechanisms is of particular importance.

Gamma/Delta T Cells in the Course of Healthy Human Pregnancy: Cytotoxic Potential and the Tendency of CD8 Expression Make CD56+ γδT Cells a Unique Lymphocyte Subset.

To date, pregnancy is an immunological paradox. The semi-allogenic fetus must be accepted by the maternal immune system, while defense against pathogens and immune surveillance cannot be compromised. Gamma/delta T cells are believed to play an important role in this immunological puzzle.

TIM-3 and TIM-1 Could Regulate Decidual TCR Bright T Cells during Murine Pregnancy.

Pregnancy is an immunological enigma where paternal antigens are present at the fetomaternal interface. What regulates the local immunotolerance, which is necessary to prevent rejection of the conceptus, is still under strong investigation. Gamma/delta T cells are believed to play a role in the local regulation of this immunotolerance towards the semiallogenic fetus.

Immune Checkpoint Molecules in Reproductive Immunology.

Immune checkpoint molecules, like CTLA-4, TIM-3, PD-1, are negative regulators of immune responses to avoid immune injury. Checkpoint regulators are thought to actively participate in the immune defense of infections, prevention of autoimmunity, transplantation, and tumor immune evasion. Maternal-fetal immunotolerance represents a real immunological challenge for the immune system of the mother: beside acceptance of the semiallogeneic fetus, the maternal immune system has to be prepared for immune defense mostly against infections.

Characteristics of peripheral blood NK and NKT-like cells in euthyroid and subclinical hypothyroid women with thyroid autoimmunity experiencing reproductive failure.

Thyroid autoimmunity (TAI) appears to play a crucial role in female infertility, recurrent pregnancy loss and IVF failure. Thyroid autoantibodies against thyroid peroxidase and thyroglobulin have been shown to represent an independent risk factor for infertility and miscarriage. Moreover, thyroxin hormone administration reduces the risk of obstetrical complications in TAI positive women.

Expansion of CD4 phenotype among CD160 receptor-expressing lymphocytes in murine pregnancy.

Problem: CD160, a cell surface co-receptor, is capable of up- or downregulating cell proliferation, cytotoxicity or cytokine production on lymphocytes. Our aim was to investigate CD160 lymphocytes in the periphery and at the maternal-foetal interface during murine pregnancy.

Method Of Study: CD4 , CD8 and gamma/delta T-cell phenotype, TIM3 co-expression and cytotoxic activity of CD160 lymphocytes of pregnant BALB/c mice were analysed by flow cytometry.

Investigation of the possible functions of PACAP in human trophoblast cells.

Pituitary adenylate cyclase activating polypeptide (PACAP) is an endogenous neuropeptide having a widespread distribution both in the nervous system and peripheral organs including the female reproductive system. Both the peptide and its receptors have been shown in the placenta but its role in placental growth, especially its human aspects, remains unknown. The aim of the present study was to investigate the effects of PACAP on invasion, proliferation, cell survival, and angiogenesis of trophoblast cells.

Involvement of Galectin-9/TIM-3 pathway in the systemic inflammatory response in early-onset preeclampsia.

Background: Preeclampsia is a common obstetrical disease affecting 3-5% of pregnancies and representing one of the leading causes of both maternal and fetal mortality. Maternal symptoms occur as an excessive systemic inflammatory reaction in response to the placental factors released by the oxidatively stressed and functional impaired placenta. The T-cell immunoglobulin domain and mucin domain (TIM) family is a relatively newly described group of molecules with a conserved structure and important immunological functions.

Cell death mechanisms and potentially cytotoxic natural immune cells in human pregnancies complicated by preeclampsia.

Preeclampsia, which occurs in about 2% to 3% of all pregnancies, is a severe multisystem disorder showing symptoms in the second half of human pregnancy. Its prevention, early diagnosis, and treatment are insufficient, since etiology and pathogenesis of the disease are still not totally understood. Recent studies confirm that preeclampsia is the extreme end of a normal inflammatory reaction, which also occurs in healthy pregnancies.

Commitment of decidual haematopoietic progenitor cells in first trimester pregnancy.

PROBLEM  The aim of this study was to investigate the phenotype and commitment of decidual haematopoietic progenitor cells (HPCs) in healthy pregnant women and in women with early miscarriage. METHOD OF STUDY  Peripheral blood and decidual tissue from healthy and pathological pregnant women were examined for HPCs and lymphoid progenitors using flow cytometric analysis. RESULTS  Compared with peripheral blood, we found a significant increase in decidual HPCs in both healthy pregnant women and women with spontaneous abortion.

Expression profiles of peripheral CD160+ lymphocytes during the course of healthy human pregnancy.

Problem: CD160 receptor is expressed by natural killer (NK) and T-cell subsets, and after activation, it could enhance cytotoxicity or pro-inflammatory cytokine production on NK cells. Here, we investigated the phenotype of peripheral CD160+ cells during healthy pregnancy.

Method Of Study: We analyzed the expression of CD69 activation marker, gamma/delta TCR, and NKG2A or NKG2D NK cell receptors on CD160+ lymphocytes of non-pregnant and healthy pregnant women at four different stages of pregnancy by flow cytometry.

Possible role of natural killer and natural killer T-like cells in implantation failure after IVF.

During implantation, maternal immunoactivation and tolerance are not only limited to the decidua but are also observed in the periphery, predominantly affecting the innate immune system. Since unexplained female infertility, as well as recurrent spontaneous abortion and implantation failure, are thought to be associated with pathological maternal immunotolerance mechanisms, this study focused on immune profile analysis of IVF candidates. Previous studies on peripheral natural killer (NK) cell characteristics of IVF patients have been limited to the comparison of blood samples taken prior to the IVF procedure.

Changes in the expression of pituitary adenylate cyclase-activating polypeptide in the human placenta during pregnancy and its effects on the survival of JAR choriocarcinoma cells.

Pituitary adenylate cyclase-activating polypeptide (PACAP), a neuropeptide with survival-promoting actions, has been observed in endocrine organs and is thought to play a role in reproductive functions, including pregnancy. PACAP occurs in two forms, 27 and 38 amino acid residues, with PACAP38 being the predominant form in human tissues. In the present study, we determined the concentrations of PACAP38 and PACAP27 in first-trimester and full-term human placentas using radioimmunoassay.

Immunoactivation in preeclampsia: Vdelta2+ and regulatory T cells during the inflammatory stage of disease.

Recent data suggest a dominant role of the innate, rather than the adaptive immune system in pregnancy-related immunoregulation. gamma/delta T cells, that comprise a minor subpopulation of human peripheral blood lymphocytes, represent a link between the innate and the acquired immune systems. However little is known about how they function in preeclampsia, which is suggested to be associated with a Th1 predominant immune response.

The role of invariant NKT cells in pre-eclampsia.

Problem: Recent data suggest a dominant role of the innate, rather than the adaptive immune system in pregnancy-related immunoregulation. Invariant NKT (iNKT) cells represent a link between the innate and the acquired immune systems; however, little is known about how they function in pre-eclampsia. The aim of our study was to investigate the possible role of iNKT cells in the pathogenesis of pre-eclampsia.

V-chain preference of gamma/delta T-cell receptors in peripheral blood during term labor.

Problem: An altered function of the maternal immune system creates a favorable environment for the developing fetus during pregnancy. At term, new regulatory mechanisms are activated, to initiate labor. Earlier we showed that in peripheral blood of pregnant women gamma/delta T cells of cytotoxic phenotype are replaced by those of a non-cytotoxic phenotype.

CD160-activating NK cell effector functions depend on the phosphatidylinositol 3-kinase recruitment.

CD160 NK cell-activating receptor is a glycosyl-phosphatidylinositol-anchored molecule that, upon specific engagement, triggers both cytotoxicity and a unique cytokine production [IFN-gamma, tumor necrosis factor-alpha (TNF-alpha) and IL-6] through an undefined signaling pathway. In the current study, we have identified several signaling molecules recruited after mAb-specific CD160 engagement in freshly isolated human circulating NK cells. Using confocal microscopy, we found that CD160 engagement induces the recruitment and co-localization of phosphorylated molecules with redistributed, capped CD160 at the cell surface.

Progesterone-dependent immunomodulation.

The biological effects of progesterone are mediated by a 34-kDa protein named the progesterone-induced blocking factor (PIBF). PIBF, synthesized by lymphocytes of healthy pregnant women in the presence of progesterone, inhibits arachidonic acid release as well as NK activity, and modifies the cytokine balance. Within the cell the full-length PIBF is associated with the centrosome, while secretion of shorter forms is induced by activation of the cell.

Cutting edge: engagement of CD160 by its HLA-C physiological ligand triggers a unique cytokine profile secretion in the cytotoxic peripheral blood NK cell subset.

CD160 is an Ig-like activating NK cell receptor expressed on the majority of circulating NK cells. This population corresponds to the nonproliferating, highly cytolytic, CD56dimCD16+ subset. CD160 engagement by HLA-C molecules mediates cytotoxic function.

Gamma/deltaT-cell subsets, NKG2A expression and apoptosis of Vdelta2+ T cells in pregnant women with or without risk of premature pregnancy termination.

Problem: Potentially cytotoxic Vdelta2+ T lymphocytes recognize human leukocyte antigen-E on the trophoblast via their CD94/NKG2A receptors. This study aims at determing the percentage of gamma/delta T-cell subsets, their NKG2A and Annexin V positivity in peripheral blood of healthy pregnant women and women at risk of premature pregnancy termination.

Method Of Study: Peripheral Vdelta2+ cells from healthy pregnant women and from women at risk of premature pregnancy termination were tested for the KIR NKG2A and Annexin V positivity by flow cytometry.

HLA-G, pre-eclampsia, immunity and vascular events.

Pre-eclampsia, one of the main complications in pregnancy, is characterised by shallow cytotrophoblast invasion of decidua as well as by vascular endothelial cell dysfunction, leading to a poor perfusion of placenta. A striking feature of pre-eclamptic pregnancies is that expression of HLA-G protein is reduced in term placentas compared with normal pregnancy. How such HLA-G deficient expression may be related to the pre-eclamptic pathology is unknown.

Engagement of CD160 receptor by HLA-C is a triggering mechanism used by circulating natural killer (NK) cells to mediate cytotoxicity.

Circulating human natural killer (NK) lymphocytes have been functionally defined by their ability to exert cytotoxic activity against MHC class I-negative target cell lines, including K562. Therefore, it was proposed that NK cells recognized the "missing self." We show here that the Ig-like CD160 receptor expressed by circulating CD56(dim+) NK cells or IL-2-deprived NK cell lines is mainly involved in their cytotoxic activity against K562 target cells.