| Abstract |
The genomic constitution of a conceptus is equally represented by the paternal and maternal counterpart. This genomic sharing includes histocompatibility antigens which during pregnancy should be recognized by the maternal organism. It is thus logical to presume that the immune system of the mother should recognize and attack the allo-MHC portion of the conceptus which should be rejected the same way paternal graft do. However, such rejection does not occur under physiological conditions. Maternal tolerance towards the semi-allogenic fetal graft is a scientific enigma that is known as the Paradox of Pregnancy. Many theories were proposed to explain this enigma. It is now generally accepted that a successful pregnancy depends not only on soluble factors circulating in the maternal serum, such as hormones, growth factors and cytokines, but also on the cellular interactions and secretion of soluble factors, occurring at a local level during the direct contact of maternal and fetal cells in the placenta. In the present study we firstly examined the serum levels of ten cytokines during the 1st, 2nd, and 3rd trimesters of pregnancy, before pregnancy and labour and compared the values of physiological first trimester of pregnancy with cases of recurrent abortion. For a long time pregnancy has been considered to be a ΤΗ2 phenomenon. According to this consideration, as expected, the TH1 cytokines did not seem to present any significant fluctuation in the different stages of pregnancy, while some of the TH2 cytokines gradually increased during pregnancy. Variation in the cytokine concentration appeared in the serum from women who aborted during their first trimester, as compared to the actual values of women in their first trimester of continuing pregnancy, suggesting that the maintenance of a balance between the production and secretion of cytokines in maternal serum is essential for a successful pregnancy. In the context of our previous studies concerning the induction of embryotoxic factors during pregnancy, we detected in the serum of pregnant mice and women, soluble class II activity. The level of soluble MHC class II antigens were increased in the serum of women after abortion. The absence of membrane class II molecules from trophoblasts is one of the crucial mechanisms that protect the embryo from typical maternal response. Despite the absence of class II antigens from the surface of trophoblasts we have identified intracellular pools of classical (HLA-DR or H-2A, in human and mice respectively) class II proteins. These intracellular pools were secreted after treatment of the cells with IFN-γ for 6 hours, indicating that IFN-γ could mobilize intracellular pools of class II MHC antigens and induce their secretion. We also detected in murine and human trophoblasts the presence of non classical MHC (HLA-DM or H-2M and HLA-DO or H-2O) antigens, as well as Invariant chain (Ii) molecules. These data in addition with the ability of trophoblast cells to express membrane class II antigens after long time induction by IFN-γ, indicate that class II antigen expression in trophoblasts is under the regulatory control of IFN-γ and that these cells can easily became antigen presenting cells and initiate the fetal rejection process.
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Ο ρόλος και οι μηχανισμοί ρύθμισης αυξητικών παραγόντων, μεμβρανικών και εκκρινόμενων τάξης ΙΙ μορίων ιστοσυμβατότητας στην επιβίωση του ημιαλλογενετικού εμβρυϊκού μοσχεύματος κατά την διάρκεια της κύησης
