STA55. Pathophysiology of preeclampsia from the view point of immunology

Abstract

Introduction The pathogenesis of preeclampsia remains largely unknown. However, many researches support the immune maladaptation hypothesis. Epidemiological findings show that first pregnancy, the use of barrier contraceptive method or short cohabitation, oocyte donation cases and obesity are the risks for preeclampsia. These factors seem to be independent. Objective We tried to explain the relationship between the epidemiological risks for preeclampsia and immune maladaptation. Method We have studied the immune system in preeclamptic cases and oocyte donation cases using flow cytometry and immunohistochemical examination. Results Human pregnancy represents a semiallograft to the maternal host, therefore tolerance system is required. In oocyte donation cases, all the MHC of the fetus are allograft to maternal host, therefore more strict tolerance system is needed. Nevertheless, our study showed the number of regulatory T (Treg) cells which induce tolerance were scare at fetomaternal interface. Moreover, macrophage, T cell and NK cells that play important roles for vascular remodeling were also scarce in placental bed biopsy samples. Importantly, vascular remodeling was inadequate in oocyte donation cases regardless of the presence or absence of preeclampsia. These findings suggest that macrophage, T cell and NK cells play an important role for vascular remodeling of spiral artery and poor placentation is present in oocyte donation pregnancy. We also showed that effector Treg cells decreased and exhausted Treg cells increased in peripheral blood of preeclampsia. Expression of Bcl-2 in Treg cells was decreased and expression of Bax in Treg cells was increased suggesting that Treg cells in preeclampsia are more likely to die by apoptosis. In our mice model, seminal plasma plays an important role for induction of paternal antigen specific Treg in the uterus. This finding explains barrier contraceptive method or short cohabitation are the risk of preeclampsia. We also showed the positive relationship between BMI and the frequencies of cytotoxic T cells and cytotoxic NK cells. Conclusion These findings support that immune maladaptation is one of the mechanisms of preeclampsia.