Dendrtic Cells Mediated Th1/Th2 Imbalance In Pathological Mechanism Of Preeclampsia

Objective: To explore the association of changes of the subsets and phenotypes of dendritic cells (DCs) in peripheral blood and uterine deciduas with Thl/Th2 type reactions in normal pregnant women and preeclamptic patients. Methods: Normal pregnant women, preeclamptic patients and nongravid women were included in the study. The DCs were stained with monoclonal antibodies against blood DCs antigens and estimated using the flow cytometric method. The cytokines were measured by ELISA methods. The numbers and subsets of DCs and serum values of cytokines were compared among the 3 groups. The mononuclear cells from peripheral blood and uterine deciduas were stimulated with rhCM-CSF and rhIL-4, the phenotypes were determined by flow cytometric method and ability of stimulating allogeneic T lymphocytes was estimated by MLR. Results: Compared with nongravid, numbers of myeloid dendritic cell (MDC) and plasmocytoid dendritic cells (PDC) slightly decreased, MDC/PDC ratio slightly increased. It was observed that the numbers of PDC and MDC were significantly lower in the second trimester, and MDC/PDC ratio was higher than in the other trimesters of physiological pregnancy. All subsets of dendritic cells and MDC/PDC ratio did not differ in the first and third trimesters of normal pregnancy. The percentage of PDC was significantly lower in preeclampsia, while MDC/PDC ratio was significantly higher in preeclamptic patients when compared with control groups. Compared with nongravid, serum IL-2 significantly decreased, IL-4,IL-10 significantly increased during 1^st trimester of pregnancy, IFN-γslightly decreased. With progressing of pregnancy, IL-2 and IL-10 statistically increased, IL-4 slightly decreased during 2^nd trimester of pregnancy, IFN-γ was similar throughout the whole pregnancy. Compared with normal pregnancies, the serum value of IL-2 and IL-10significantly increased in preeclamptic patients, IL-4 significantly decreased, IL-2/IL-10 ratio decreased and IFN-γ / IL-10 ratio increased. CD205 positive dendritic cells sparsely existed in the deciduas of 1^st and 3^rd trimester of gestation, and the mean density of CD205+ was about 1% in all of the mononuclear cell. There were more DCs and MDC in deciduas than in peripheral blood, the ratio of MDC/PDC was also higher in deciduas. Compared with normal pregnancy, there much more DCs and MDC in preeclamptic pregnancy, but the number was not changed in different gestation stage. There were much more DCs and MDC in the preeclamptic deciduas, the ratio of MDC/PDC was also significant higher in the preeclamptic patients than in normal pregnancy. Like dendritic cells in peripheral blood, DCs in deciduas were also can be induced by rhGM-CSF and rhIL-4, and also has the ability to stimulate allogeneic T lymphocytes proliferation. After cultured for 9 days, all cell population from peripheral blood and deciduas population exhibited a typical DC morphology, were nonadherent, of approximately 10 μm in diameter, and with an irregularly shaped cell body. They were characterized by a varying number of long dendrites on their surface which continually extended, retracted, and bent in many directions giving a characteristic veiled appearance. Flow cytometric analysis of the cultured cell population demonstrated that all cells expressed CD80, CD83, CD86 and HLA-DR, didn't or rarely express Lineage. We next compared the ability of decidual DCs and blood PMBC-derived DCs to stimulate the proliferation of allogeneic T cells. Similar to PMBC-derived DCs, decidual DCs also had the ability to stimulate T cells proliferation. But the ability of stimulation was stronger in preeclamptic patient's peripheral blood and deciduas origining DCs, level of IL-10 decreased and IL-12 increased in preeclamptic patient's culture medium than normal pregnancy. Conclusion: Th2 type cytokines were predominant in peripheral blood and maternal-fetal interface during physiological gestation, while Th1 type cytokines were predominant in preeclamptic pregnancy, dendritic cells subsets changed during the three trimester of physiological and preeclamptic pregnancy consistent with Th1/Th2 cytokines. Dendric cells also existed in deciduas and had the similar phenotype and ability of immuneregulatory to the DCs in peripheral blood. Dendric cells in deciduas and peripheral blood may be involved in the immune regulation during physiological pregnancy, it seems possible that changes of subset and phenotype of DCs may be associated with increased Th1-type immunity in patients with preeclampsia.