Immunological Profiling of CD8 and CD8 NK Cell Subpopulations and Immune Checkpoint Alterations in Early-Onset Preeclampsia and Healthy Pregnancy.

Despite the numerous studies on the clinical aspects of early-onset preeclampsia, our understanding of the immunological consequences of inadequate placenta development remains incomplete. The Th1-predominance characteristic of early-onset preeclampsia significantly impacts maternal immunotolerance, and the role of immune checkpoint molecules in these mechanisms is yet to be fully elucidated. Our study aims to fill these crucial knowledge gaps.

The Influence of Early Onset Preeclampsia on Perinatal Red Blood Cell Characteristics of Neonates.

Preeclampsia is the leading cause of complicated neonatal adaptation. The present investigation aimed to study the hemorheological factors during the early perinatal period (cord blood, 24 and 72 h after delivery) in newborns of early-onset preeclamptic mothers ( = 13) and healthy neonates ( = 17). Hematocrit, plasma, and whole blood viscosity (WBV), red blood cell (RBC) aggregation, and deformability were investigated.

CD8 and CD4 Positive NKT Subpopulations and Immune-Checkpoint Pathways in Early-Onset Preeclampsia and Healthy Pregnancy.

Although many studies have investigated the clinical aspect of early-onset preeclampsia, our knowledge about the immunological consequences of improper placenta development is scarce. The maternal immunotolerance against the fetus is greatly influenced by the Th1 predominance developed by the mother's immune system. Thirty-two early-onset preeclamptic and fifty-one healthy pregnant women with appropriately matched gestational age were involved in our study.

Examination of the TIGIT-CD226-CD112-CD155 Immune Checkpoint Network during a Healthy Pregnancy.

The importance of immune checkpoint molecules is well known in tumor and transplantation immunology; however, much less information is available regarding human pregnancy. Despite the significant amount of information about the TIGIT and CD226 immune checkpoint receptors in immune therapies, very little research has been conducted to study the possible role of these surface molecules and their ligands (CD112 and CD155) during the three trimesters of pregnancy. : From peripheral blood, immune cell subpopulations were studied, and the surface expression of immune checkpoint molecules was analyzed by flow cytometry.

CD8+ and CD8- NKT Cells Exhibit Phenotypic Changes During Pregnancy.

Background: NKT cell population is a relatively well-characterized immune cell subset. Numerous publications have characterized the phenotypical features of its subpopulations even in human pregnancy. Nevertheless, there have not been studies investigating the distribution of the NKT cells based on the surface presence of the CD8 receptor.

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.

Examination of the TIGIT, CD226, CD112, and CD155 Immune Checkpoint Molecules in Peripheral Blood Mononuclear Cells in Women Diagnosed with Early-Onset Preeclampsia.

Early-onset preeclampsia is a common obstetrical disease with a potential genetic background and is characterized by the predominance of Th1 immune response. However, although many studies investigated the immunological environment in preeclamptic patients, no information is available about the potential role of the TIGIT/CD226/CD112/CD155 immune checkpoint pathway. A total of 37 pregnant women diagnosed with early-onset preeclampsia and 36 control women with appropriately matched gestational age were enrolled in this study.

Peripartum Investigation of Red Blood Cell Properties in Women Diagnosed with Early-Onset Preeclampsia.

We investigated peripartum maternal red blood cell (RBC) properties in early-onset preeclampsia (PE). Repeated blood samples were taken prospectively for hemorheological measurements at PE diagnosis (n = 13) or during 26-34 weeks of gestation in healthy pregnancies (n = 24), then at delivery, and 72 h postpartum. RBC aggregation was characterized by M index (infrared light transmission between the aggregated RBCs in stasis) and aggregation index (AI-laser backscattering from the RBC aggregates).

Influence of Galectin-9 Treatment on the Phenotype and Function of NK-92MI Cells in the Presence of Different Serum Supplements.

Galectins are one of the critical players in the tumor microenvironment-tumor crosstalk and the regulation of local immunity. Galectin-9 has been in the limelight in tumor immunology. Galectin-9 possesses its multiplex biological functions both extracellularly and intracellularly, plays a pivotal role in the modulation of adaptive and innate immunity, and induces immune tolerance.

Forest Bathing Always Makes Sense: Blood Pressure-Lowering and Immune System-Balancing Effects in Late Spring and Winter in Central Europe.

Various formats of forest bathing have been receiving increasing attention owing to their perspectives in health promotion and the treatment of chronic lifestyle diseases. The majority of field studies are still being conducted in the Far Eastern region, and they often make psychological assessments mainly in the green season. In our pretest-posttest field experiment, twelve healthy, working-age volunteers participated in a 2-h leisurely forest walking program, first in the green season (May) and then in the winter season (January), in the Mecsek Hills, next to Pécs, Hungary.

Investigation of the PD-1 and PD-L1 Immune Checkpoint Molecules Throughout Healthy Human Pregnancy and in Nonpregnant Women.

: A growing body of evidence supports the importance of PD-1 and PD-L1, especially in the materno-fetal interface, although limited information is available about the peripheral expression of these molecules during the trimesters of pregnancy. : 13 healthy women were enrolled from the 1st, 10 from the 2nd and 12 from the 3rd trimester of pregnancy at the same time, 10 healthy, age-matched nonpregnant women formed the control group. From peripheral blood, mononuclear cells were separated and stored at -80 °C.

Investigation of mucosal-associated invariant T (MAIT) cells expressing immune checkpoint receptors (TIGIT and CD226) in early-onset preeclampsia.

Objective: During our work, we examined the possible contribution of MAIT cells in the pathogenesis of the clinical phase of early-onset preeclampsia and how this could be influenced by TIGIT and CD226 immune checkpoint molecules.

Study Design: 37 pregnant women diagnosed with early-onset preeclampsia and 36 healthy, age-matched control women were involved in this study. Peripheral blood mononuclear cells were isolated by density gradient and frozen.

Different Expression Pattern of TIM-3 and Galectin-9 Molecules by Peripheral and Peritoneal Lymphocytes in Women with and without Endometriosis.

Endometriosis is a gynecological condition that is associated with chronic pelvic inflammation, pain, and infertility. Although substantial evidence supports that immunological alterations contribute to its pathogenesis and we previously posed a pivotal role of Galectin-9 (Gal-9) in this disorder, the involvement of the TIM-3/Gal-9 pathway in the development of endometriosis-associated immunological abnormalities is not yet known. In the present study, multicolor flow cytometry was used to compare the immunophenotype and cell surface expression of TIM-3 and Gal-9 molecules on peripheral blood (PB) and peritoneal fluid (PF) lymphocytes of women with and without endometriosis.

Direct-acting antiviral treatment downregulates immune checkpoint inhibitor expression in patients with chronic hepatitis C.

Chronic hepatitis C (CHC) infection is associated with increased TIM-3, PD-1 immune checkpoint receptors expression that inhibits adaptive T cells and increases NK cell cytotoxicity against T helper cells, both resulting T cell exhaustion. Elimination of the virus with direct-acting antivirals (DAAs) may modify host immune response via altering these immune checkpoint receptors' expression. We conducted a prospective study to analyze changes in TIM-3, PD-1 and their ligands galectin-9, PD-L1 expression by peripheral blood T cell subpopulations, NK cell subpopulations, and monocytes by multicolor flow cytometry in 14 CHC patients successfully treated with 12 weeks of dasabuvir, ombitasvir, and paritaprevir/ritonavir plus ribavirin.

Phenotypic characterization of testicular immune cells expressing immune checkpoint molecules in wild-type and pituitary adenylate cyclase-activating polypeptide-deficient mice.

Problem: Pituitary adenylate cyclase-activating polypeptide (PACAP) is a neuropeptide having several regulatory functions in the nervous system and in peripheral organs including those of the reproductive system. PACAP-deficient male mice have several morphological, biochemical, behavioral defects and show disturbed signaling in spermatogenesis affecting fertility in PACAP KO mice. Reproductive functions such as fertility, mating, and maternal behaviors have been widely investigated, but no immune analyses are available regarding the testicular immune-privileged environment in male PACAP-deficient mice.

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.

The importance of the PD-1/PD-L1 pathway at the maternal-fetal interface.

Background: Our goal with this study was to investigate the contribution of PD-1/PD-L1 immune-checkpoint pathway to maternal immunotolerance mechanisms.

Methods: Thirteen healthy pregnant women and 10 non-pregnant controls were involved in this project. PBMCs and DICs were isolated from peripheral blood and from decidual tissues.

Involvement of the PD-1/PD-L1 Co-Inhibitory Pathway in the Pathogenesis of the Inflammatory Stage of Early-Onset Preeclampsia.

The programmed cell death protein 1 (PD-1) receptor has been reported to downregulate T cell activation effectively via binding to its ligands PD-L1 or PD-L2 in a negative co-stimulatory manner. Little is known about the involvement of PD-1 mediated immunoregulation in pregnancy and in pregnancy-related disorders. In this work, we investigated the possible role of the PD-1 co-stimulatory pathway in the pathogenesis of the clinical phase of early-onset preeclampsia characterized by a systemic maternal inflammatory response.

Antioxidant and antimicrobial properties of randomly methylated β cyclodextrin - captured essential oils.

Free essential oils and their active components have a low physiochemical stability and low aqueous solubility which limit their applications as food preservatives and in packaging industry. The aim of this study was to characterize the physicochemical properties, antioxidant activities and antimicrobial activity of randomly methylated β cyclodextrin (RAMEB) encapsulated thyme oil, lemon balm oil, lavender oil, peppermint oil and their active components that include thymol, citral, linalool, menthol and borneol. Inclusion complex formation of essential oils (EOs) and RAMEB were evaluated by several methods.

Comparative analysis of decidual and peripheral immune cells and immune-checkpoint molecules during pregnancy in wild-type and PACAP-deficient mice.

Problem: PACAP is a neuropeptide having a major relevance in the nervous system and in several peripheral organs including those of the reproductive system. PACAP-deficient mice have several morphological, biochemical, behavioral defects, and show reduced fertility. Female reproductive functions such as fertility, mating behavior, maternal behaviors, and implantation alterations have been widely investigated, but no comparative immune analyses are available in pregnant wild-type (WT) and PACAP knockout (KO) mice.

The immunological effect of Galectin-9/TIM-3 pathway after low dose Mifepristone treatment in mice at 14.5 day of pregnancy.

The abortifacient Mifepristone (RU486) has proven to be a safe, effective, acceptable option for millions of women seeking abortion during the first and second trimester of pregnancy although its precise mechanism of action is not well understood. The main objective of this study was to investigate the impact of low dose Mifepristone administration on placental Galectin-9 (Gal-9) expression, as well as its effect on the cell surface expression of Gal-9, TIM-3 and CD107a molecules by different T and NK cell subsets. A model of Mifepristone-induced immunological changes was established in syngeneic pregnant BALB/c mice.

The possible role of CD8+/Vα7.2+/CD161++ T (MAIT) and CD8+/Vα7.2+/CD161 T (MAIT-like) cells in the pathogenesis of early-onset pre-eclampsia.

Problem: The objective of this study was to compare the expressions of different immune-checkpoint molecules by MAIT and MAIT-like cells in healthy pregnancy and in early-onset pre-eclampsia.

Method Of Study: Peripheral blood mononuclear cells (PBMC) were stained with monoclonal antibodies to characterize MAIT and MAIT-like cells. Flow cytometric analyses were used to measure PD-1, TIM-3, activation markers, and intracellular perforin expression.

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.