O-90:Dendritic Cells And Pregnancy:A Bidirectional Relationship ToProtect The Semiallogenic Fetus



Dendritic cells (DCs) constitute a system of antigen presenting cells (APC) that are key regulators of immune responses. DCs are not only critical for induction of primary immune responses, but depending on their subsets and their maturation state may also be important for the induction of immunological tolerance, as well as for the regulation of T cell – mediated cytokine profiles. Regarding the importance of Th2 immunity as well as induction of tolerance to fetal allograft during pregnancy and having considered the mutual role of DCs in induction of immunity vs. tolerance and Th1 vs. Th2 immune responses, it seems that these cells could be potentially suitable candidate that mediate the balance of maternal immune responses to support pregnancy. To address this issue we set out a series of studies concerning the role of DCs in indispensable immuneregulation during successful pregnancy and the effects of pregnancy related soluble factors (hormones, cytokines etc.) on DCs. First of all we evaluated the frequency, localization and immunophenotype of murine endometrial DCs during different stages of estrous cycle. In addition, to address the systemic effect of hormonal fluctuations during estrous cycle, the same variables were studied in splenic DCs. The second study was performed to evaluate the kinetics of endometrial DC subsets at different stages of murine pregnancy. To address the systemic effect of pregnancy on DC kinetic, the same variables were also studied in splenic DC populations. The third study was set out to show the effects of soluble factors released in the supernatant of murine decidual cell cultures on the capacity of dendritic cells to present antigens in-vivo and on their ability to induce cytokine production by primed lymphocytes. We also investigated the immunosuppressive effect of pregnant mouse serum on allostimulatory activity of DCs to determine how activity of DCs could be affected during pregnancy. Regarding the pivotal role of Indoleamine 2, 3 dioxygenase (IDO) enzyme in pregnancy and considering that DCs are one of the main sources of this enzyme, the next studies were performed to investigate the effects of pregnant serum and decidual microenvironment on IDO induction in DCs and the role of IDO in DCs induced immunoregulation. Various methods including: cell separation methods (mostly splenic DCs and lymph node T cells), cell and tissue culture methods, Mixed leukocyte reaction(MLR), lymphocyte transformation test(LTT), ELISA, cytochemical and immunohistochemical methods, morphometric analysis, flow cytometry, HPLC etc. were used to perform these studies. Our data demonstrate that the balance of DCs subsets is finely tuned throughout estrous cycle and pregnancy. The frequency of endometrial DCs is highest at estrus, a phase in estrous cycle in which mating occurs and copulation is associated with further recruitment of large numbers of DCs in to the early deciduas, pointing an eminent immunoregulatory role of DCs in maintenance of pregnancy. It seems that soluble factors produced by decidual cells are important mediators of immunoregulation at the fetomaternal interface which provide the two fundamental requirements for protection of semiallogenic fetus, namely immunologic tolerance and predominance of Th2 immunity, through modulation of DCs function. Pretreatment of DCs with supernatant from decidual cultures but not pregnant serum significantly induces IDO expression while both treatments inhibit their capacity to induce production of TH1 cytokines and allogenic T cell allostimulatory capacity. Abstract of the 8th Royan International Twin Congress, Tehran, Iran, 5-7 September 2007 Yakhteh Medical Journal, Vol 9, Sup 1, Summer 2007 53 In conclusion, it can be postulated that DCs are key regulators of immune system during pregnancy and bidirectional relation of DCs and pregnancy protects the semiallogenic fetus from immunologic rejection. Such information may provide the basis for better understanding of female genital tract-immunity and may shed light on the way through which immunologically supporting microenvironment is organized for pregnancy maintenance.