Leukocytes at the maternal-fetal interface in human pregnancy

The aim of this thesis was to gain a better understanding of the immunoregulatory mechanisms associated with maternal tolerance of the fetus during pregnancy. The distribution of decidual leukocytes, specifically uterine NK cells and T cells, in the decidua basalis and parietalis were studied in the setting of normal term pregnancy, following elective cesarean section or spontaneous vaginal delivery, in the setting of complicated pregnancy, and in the setting of assisted reproduction, and to study the function of term decidual leukocytes, specifically proliferation and cytokine production, in response to fetal and allogeneic blood leukocytes. Techniques involving flow cytometry, immunohistochemistry and mixed lymphocyte cultures were used to perform these studies.LEI Universiteit LeidenStichting Fetal Maternal Research J.E.Jurriaanse Stichting Dr. Ir. van de Laar Stichting Medical Dynamics Wyeth Pharmaceuticals Novartis Pharma Innogenetics DiaMed BeneluxFoetale geneeskunde, in het bijzonder reproductieve immunologi

Regulatory T-cells and immune tolerance in pregnancy: a new target for infertility treatment?

BACKGROUND: Adaptation of the maternal immune response to accommodate the semi-allogeneic fetus is necessary for pregnancy success, and disturbances in maternal tolerance are implicated in infertility and reproductive pathologies. T regulatory (Treg) cells are a recently discovered subset of T-lymphocytes with potent suppressive activity and pivotal roles in curtailing destructive immune responses and preventing autoimmune disease. METHODS: A systematic review was undertaken of the published literature on Treg cells in the ovary, testes, uterus and gestational tissues in pregnancy, and their link with infertility, miscarriage and pathologies of pregnancy. An overview of current knowledge on the generation, activation and modes of action of Treg cells in controlling immune responses is provided, and strategies for manipulating regulatory T-cells for potential applications in reproductive medicine are discussed. RESULTS: Studies in mouse models show that Treg cells are essential for maternal tolerance of the conceptus, and that expansion of the Treg cell pool through antigen-specific and antigen non-specific pathways allows their suppressive actions to be exerted in the critical peri-implantation phase of pregnancy. In women, Treg cells accumulate in the decidua and are elevated in maternal blood from early in the first trimester. Inadequate numbers of Treg cells or their functional deficiency are linked with infertility, miscarriage and pre-eclampsia. CONCLUSIONS: The potency and wide-ranging involvement of Treg cells in immune homeostasis and disease pathology indicates the considerable potential of these cells as therapeutic agents, raising the prospect of their utility in novel treatments for reproductive pathologies.Leigh R. Guerin, Jelmer R. Prins and Sarah A. Robertso

Preservation of human placenta facilitates multicenter studies on the local immune response in normal and aberrant pregnancies

<p>Our standard procedure for phenotypic and functional analysis of immune cells present in the placenta is to isolate leukocytes from the decidua within five hours of the delivery. However, this results in logistical problems with deliveries at night, weekends or in other medical centers. Collecting placentas after complicated pregnancies is even more difficult owing to the low prevalence and the often unscheduled delivery. The aim was to investigate the possibility of preserving the human placenta before phenotypic and functional analysis of decidual lymphocytes. Placentas were obtained after uncomplicated pregnancy. The tissue was divided into two equal parts: decidual lymphocytes from one part were isolated within five hours according to our standard procedure, whereas the other part was preserved in either Celsior (R), a storage solution for solid organ preservation, or phosphate-buffered saline (PBS) for 24 h at 4 degrees C before isolation. Overall, the phenotype and functional capacity of decidual lymphocytes isolated within five hours was comparable to decidual lymphocytes isolated after 24-h preservation in Celsior (R) or PBS. Minor differences were found between decidual lymphocytes isolated within five hours and decidual lymphocytes isolated after 24-h preservation in Celsior (R). The results indicate that PBS is sufficient to preserve the placenta for 24h for phenotypical and functional studies. The ability to preserve the placenta will simplify the procedure for the isolation of decidual lymphocytes and makes it easier to analyze tissue from women who deliver during the night, at weekends or in other hospitals, and possibly even women with complicated pregnancies. (C) 2013 Elsevier Ireland Ltd. All rights reserved.</p>

Human Labor Is Associated with Reduced Decidual Cell Expression of Progesterone, But Not Glucocorticoid, Receptors

Context: Unchanging plasma progesterone (P4) levels suggest that human labor is initiated by reduced P4 receptor (PR) expression, which elicits functional P4 withdrawal. The glucocorticoid receptor (GR) is also implicated in this process

Changes in the Ratio of Tc1/Tc2 and Th1/Th2 Cells but Not in Subtypes of NK-Cells in Preeclampsia

It has been suggested that natural killer (NK) cell activity and Th1 immunitymay be involved in the pathogenesis of preeclampsia. This study aimed to investigate theimmunophenotypes of NK cells and type 1/type 2 immunity in both decidua and maternalperipheral blood between normal (n=11) and preeclamptic pregnant women (n=20) by flowcytometry. The results showed that no significant difference was observed between patientsand controls by detecting CD56+ CD69+ and CD56+ CD94+ NK cells in both peripheralblood and decidua. Moreover, in preeclamptic patients, decreased percentages of Tc2 andTh2 cells and the increased ratios of Tc1/Tc2 were determined in both decidua andmaternal peripheral blood. In addition, the ratio of Th1/Th2 in peripheral blood alsoincreased. There was no significant difference of immunophenotypes of uNK cells betweenpreeclampsia and normal pregnancy. Local decidua and systematic immunity did notcorrelate with each other. These results suggest that the type 1/type 2 immunity shifted totype 1 immunity including Th1 and Tc1 cells may contribute to the patho-genesis ofpreeclampsia