IFPA Meeting 2011 workshop report III: Placental immunology; epigenetic and microRNA-dependent gene regulation; comparative placentation; trophoblast differentiation; stem cells (original) (raw)
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Feto–maternal immune interaction at the placental level
Lupus, 2004
A special interaction is established during pregnancy between the maternal immune system and fetal cells to allow the survival and the normal growth of the fetus. Fetal cells expressing paternal alloantigens are not recognized as foreign by the mother because of an efficient anatomic barrier and a local immunosuppression determined by the interplay of locally produced cytokines, biologically active molecules and hormones. A special balance between TH1 and TH2 lymphocytes has also been observed at the feto -maternal barrier that contribute to control the immune response at this level. An important role is played by trophoblast cells that act as a physical barrier forming a continuous layer and exert immunomodulatory function. Trophoblast cells have also been shown to express regulators of the complement system and to downregulate the expression of HLA antigens. Dysfunction of these cells leads to morphological and functional alterations of the feto -maternal barrier as well as to hormonal and immune imbalance and may contribute to the development of pathologic conditions of pregnancy, such as recurrent spontaneous abortions. Efforts are still needed to better understand the physiology of the feto -maternal interaction and the pathogenetic mechanisms responsible for tissue damage in pathologic conditions of pregrancy. Lupus (2004) 13, 1-5.
Immune cells in the placental bed
The International Journal of Developmental Biology, 2010
Leukocytes are an important component of the human uterine decidua in normal pregnancy. The focus of research has been on the more abundant populations such as the uterine natural killer (uNK) cells and macrophages, but more recently interest has also extended to less abundant, but functionally significant populations. Investigation of function in human pregnancy is limited by the scope of in vitro studies and the inability to perform in vivo manipulation of cell populations. Investigation of pathological pregnancy may provide clues to function, although acquisition of samples is limited until after clinical presentation. Investigation of animal models may provide clues to function in humans and this has certainly been the case for the uNK cells. However, human placentation differs substantially from the usual laboratory animal models and any extrapolation to humans from animal studies should be made with this in mind. Considerable advances have been made over the last 25 years but many questions still remain; the next 25 years may provide more answers to the role of the endometrial leukocytes in normal pregnancy, so that further advances can be made in investigation of their role, if any, in pregnancy pathology.
Immunology of pregnancy: towards a unifying hypothesis
European Journal of Obstetrics & Gynecology and Reproductive Biology, 1992
The variable findings of hormonal-immunoregulation and the variable cellular and humoral immune responses in pregnancy have been considered in relationship to the physiological response. From such considerations it appears that the peripheral blood lymphocyte/leukocyte response in pregnancy is not important, but rather the local uterine immune response at implantation and throughout pregnancy. It is proposed, and evidence is presented, that a normal allogeneic immune response is initiated at the time of implantation of the blastocyst. This immune response regulates the invasive nature of the trophoblast and initiates the first stage of parturition. The initiation and maintenance of this immune response is based on an interplay between maternal and paternal HLA and trophoblast antigens. In the case of HLA-incompatible donor-recipient blastocyst transplants, a more pivotal role for immunoregulation by trophoblast antigens is proposed. This is because it is considered that the local uterine immune response suppresses the expression of allogeneic HLA. This concept is further developed in terms of haploid HLA suppression on maternal and fetal lymphocytes that cross the placenta. This is considered to allow the interaction of these lymphocytes with each other and explains maternal transfer of cell-mediated immunity.
PLoS ONE, 2014
Pregnancy poses a unique challenge to the human immune system: the semi-allogeneic fetus must be protected from maternal immune attack while immunity towards pathogens is maintained. Breakdown in maternal-fetal tolerance can lead to pregnancy-specific diseases with potentially high degrees of morbidity and mortality for both the mother and her fetus. Various immune cell-types could mediate these functions, but a comprehensive evaluation of the peripheral and local maternal T cell and regulatory T cell compartments in normal human pregnancy is lacking. In this case-control study, we apply the Human Immunology Project Consortium proposed gating strategies to samples from healthy 3 rd trimester human subjects compared with healthy non-pregnant controls. The proportions of HLA-DR+ and CD38+ effector-and effector memory CD8 T cells are significantly increased in the peripheral blood of pregnant women. Utilizing a novel technique that takes advantage of the standard protocol for intrauterine cleanup after cesarean section, we isolate lymphocytes resident at the uteroplacental interface (UPI). At the UPI, the CD4 and CD8 T cell compartments largely mirror the peripheral blood, except that the proportion of HLA-DR+ activated T regulatory cells is significantly increased in direct proportion to an observed increase in the number of activated CD8 T cells. We find that cryopreservation and delayed sample processing (. 12 hours) decreases our ability to identify regulatory T cell subsets. Further, the Consortium proposed method for Treg identification underrepresents Resting and Cytokine Tregs compared with Activated Tregs, thus skewing the entire population. Better understanding of the changes in the immune system during pregnancy in the peripheral blood and at the uteroplacental interface are essential for progress in treatment of pregnancy diseases such as pre-eclampsia and recurrent miscarriage.
Immune cells and molecules in pregnancy: friends or foes to the fetus?
Expert Review of Clinical Immunology, 2006
Considering allograft rejection as a basic feature of the immune system, the mammalian pregnancy is an immunological paradox where the semi-allogeneic fetus is not rejected. How are the demands of pregnancy solved in the context of maternal immunity? Medawar's original proposal of maternal immune inertness during pregnancy should be revised to active materno-placental tolerance. Multiple mechanisms are involved in peripheral and local tolerance induction that prevents fetal rejection while maintaining competent immune surveillance and protection. The goal of this review is to discuss the major cellular and molecular components of the immune system that control and promote fetal survival.
Pregnancy and the immune system: between tolerance and rejection
Toxicology, 2003
Interactions between the conceptus and the mother are bi-directional: the feto-placental tissues need nutrition and a suitable environment in homeostatic condition whereas the mother influenced by the placental factors adapts her metabolism and immune system. Many different mechanisms acting locally or at distance ensure tolerance of the semi-allogeneic graft by the maternal natural and adaptive immune defences. In front of this tolerance, mechanisms exist ensuring rejection of the conceptus by the mother (spontaneous abortion) through rupture of one or more tolerance mechanisms, notably in stress situations endangering the mother. Thus outcome of a pregnancy is dependent on efficiently working tolerance mechanisms, and rupture of such mechanisms can lead to rejection. The balance of influence leading either to tolerance or rejection is under control of internal (maternal and fetal) and external (environmental) factors. Rejection, if triggered, mainly occurs through immune-induced i...
2012
The mammalian pregnancy is an immunologic challenge to the maternal immune system. Considering the fact that transplant rejection is a well-defined immunologic phenomenon, the peaceful feto-maternal coexistence during mammalian pregnancy has been defined as “a paradox of nature” and puzzled immunologists for ages. In 1953, the immunologist and Nobel Prize laureate Sir Peter Medawar proposed that the maternal immune system is ignoring the fetus and defined his three well-known mechanisms for achievement of this: anatomical separation of the fetus and the mother, fetal antigenic immaturity and maternal inertness or indolence to the fetus (1). Although Medawar’s proposal is still recognized and cited, it is only partly true and has been rightly revised in recent years. Today, it is wellproven that instead of being ignored, pregnancy is indeed recognized but tolerated by the maternal immune system, however, the responsible mechanisms for that remain unknown. The maternal-fetal interacti...
Journal of Reproductive Immunology, 2013
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 ® , a storage solution for solid organ preservation, or phosphatebuffered saline (PBS) for 24 h at 4 • 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 ® or PBS. Minor differences were found between decidual lymphocytes isolated within five hours and decidual lymphocytes isolated after 24-h preservation in Celsior ®. The results indicate that PBS is sufficient to preserve the placenta for 24 h 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.