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.

/pdf/regulatory-t-cells-and-immune-tolerance-in-pregnancy-a-new-5dolejlpmc.pdf

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

Implantation is a key stage during pregnancy, as the fate of the embryo is often decided upon its first contact with the maternal endometrium. Around this time, DCs accumulate in the uterus; however, their role in pregnancy and, more specifically, implantation, remains unknown. We investigated the function of uterine DCs (uDCs) during implantation using a transgenic mouse model that allows conditional ablation of uDCs in a spatially and temporally regulated manner. Depletion of uDCs resulted in a severe impairment of the implantation process, leading to embryo resorption. Depletion of uDCs also caused embryo resorption in syngeneic and T cell–deficient pregnancies, which argues against a failure to establish immunological tolerance during implantation. Moreover, even in the absence of embryos, experimentally induced deciduae failed to adequately form. Implantation failure was associated with impaired decidual proliferation and differentiation. Dynamic contrast-enhanced MRI revealed perturbed angiogenesis characterized by reduced vascular expansion and attenuated maturation. We suggest therefore that uDCs directly fine-tune decidual angiogenesis by providing two critical factors, sFlt1 and TGF-β1, that promote coordinated blood vessel maturation. Collectively, uDCs appear to govern uterine receptivity, independent of their predicted role in immunological tolerance, by regulating tissue remodeling and angiogenesis. Importantly, our results may aid in understanding the limited implantation success of embryos transferred following in vitro fertilization.

/pdf/uterine-dcs-are-crucial-for-decidua-formation-during-embryo-4yw39khxgl.pdf

Uterine DCs are crucial for decidua formation during embryo implantation in mice

T regulatory (Treg) cells are implicated in maternal immune tolerance of the conceptus at implantation; however, the antigenic and regulatory signals controlling Treg cells in early pregnancy are undefined. To examine the role of male seminal fluid in tolerance induction, the effect of exposure to seminal fluid at mating on responsiveness to paternal alloantigens was examined using paternal tumor cell grafts and by delayed-type hypersensitivity (DTH) challenge on Day 3.5 postcoitum. Exposure to seminal fluid inhibited rejection of paternal tumor cells, independently of fertilization and embryo development, while seminal fluid from major histocompatability complex (MHC)-dissimilar males was less effective. Similarly, mating with intact males suppressed the DTH response to paternal alloantigens in an MHC-specific fashion. Excision of the seminal vesicle glands diminished the tolerance-inducing activity of seminal fluid. Mating with intact males caused an increase in CD4+CD25+ cells expressing FOXP3 in the para-aortic lymph nodes draining the uterus, beyond the estrus-associated peak in cycling mice. The increase in CD4+CD25+ cells was abrogated when males were vasectomized or seminal vesicles were excised. Collectively, these data provide evidence that exposure to seminal fluid at mating promotes a state of functional tolerance to paternal alloantigens that may facilitate maternal acceptance of the conceptus at implantation, and the effects of seminal fluid are likely to be mediated by expansion of the Treg cell pool. Both seminal plasma and sperm components of the seminal fluid are necessary to confer full tolerance and elicit the Treg cell response, potentially through provision of immune-deviating cytokines and antigens, respectively.

/pdf/seminal-fluid-drives-expansion-of-the-cd4-cd25-t-regulatory-1ddodsfao5.pdf

Seminal Fluid Drives Expansion of the CD4+CD25+ T Regulatory Cell Pool and Induces Tolerance to Paternal Alloantigens in Mice

Posttraumatic growth in cancer: reality or illusion?

Piscine macrophage aggregates: A review

Pregnancy is a unique event in which a fetus, despite being genetically and immunologically different from the mother (a hemi-allograft), develops in the uterus. Successful pregnancy implies avoidance of rejection by the maternal immune system. Fetal and maternal immune cells come into direct contact at the decidua, which is a highly specialized mucous membrane that plays a key role in fetal tolerance. Uterine dendritic cells (DC) within the decidua have been implicated in pregnancy maintenance. DC serve as antigen-presenting cells with the unique ability to induce primary immune responses. Just as lymphocytes comprise different subsets, DC subsets have been identified that differentially control lymphocyte function. DC may also act to induce immunologic tolerance and regulation of T cell-mediated immunity. Current understanding of DC immunobiology within the context of mammalian fetal-maternal tolerance is reviewed and discussed herein.

Dendritic Cells: Key to Fetal Tolerance?

Immune systems and responses in Monotremata and Marsupialia are reviewed. The Monotremata (Prototheria) are egg-laying mammals. Few studies have been carried out on monotremes. The structure of the lymph nodules of Tachyglossus aculeatus is unusual, and the occurrence of IgG in this species is noteworthy: IgG has not yet been found in any non-mammal.

A number of Marsupialia (Metatheria) species have been used as immunological models. Generally immune responses are somewhat slower and less accentuated than in placental (eutherian) mammals. Of interest is the presence of cervical and thoracic thymuses in several marsupials. Marsupials are born very immature and possess rather rudimentary immune responses at birth: the neonate may provide a helpful model for immune ontogenesis. Marsupials have a full repertoire of immunoglobulin classes. MHC Class II (but not Class I) gene polymorphism may be limited. Studies using molecular biology techniques are awaited to elucidate the structural organization of the immune components and to determine similarities and differences between marsupials' and other animals' immune systems.

"Not proper mammals": immunity in monotremes and marsupials.

Committee on education

A field investigation into the effect of sewage effluent and general water quality on selected immunological indicators in carp (Cyprinus carpioL.)

Publisher Summary This chapter focuses on the immune response in teleost and anuran. The Teleostei are the dominant fish fauna in marine and freshwater ecosystems today. Although the Anura are not dominant in terrestrial ecosystems, they are, nevertheless, a successful order with many species, well adapted to a variety of habitats. Among the Osteichthyes and the Amphibia, the Teleostei and the Anura are the most advanced and highly evolved living forms, both groups having radiated extensively during their phylogenetic history. The Teleostei are of considerable economic importance, and an understanding of teleosteans' immune systems, as it pertains to their ability to resist infection, is of great interest to fisheries. The adult frog or toad is an easily maintained organism whose general physiology is well understood, and the tadpole represents a free-living, accessible larva open to experimental manipulation. Xenopus laevis has, arguably, the most completely investigated immune system of any poikilotherm.

Richard D. Jurd

Papers

Dendritic Cells: Key to Fetal Tolerance?

"Not proper mammals": immunity in monotremes and marsupials.

Committee on education

A field investigation into the effect of sewage effluent and general water quality on selected immunological indicators in carp (Cyprinus carpioL.)

Specialisation in the teleost and anuran immune response: a comparative critique