Human chorionic gonadotropin and luteinizing hormone, but not progesterone, contribute to the initiation of a tolerogenic immune response in pregnancy (P3216)

Abstract

Abstract The survival of the fetus in the maternal uterus is ensured by both intensive hormonal changes and a protective maternal immune response towards the fetus. We have recently reported that human Chorionic Gonadotropin (hCG) facilitates the migration of Treg to the fetal-maternal interface and supports their tolerogenic function. The role of hormones in the establishment of an antigen-specific immune response is however not well understood. Here, we investigated the effect of pregnancy hormones on the maturation state of DCs and their functionality in a model of spontaneous abortion due to disturbed tolerance. Pregnant females were treated either with hCG, Luteinizing Hormone (LH), Progesterone (P) or PBS. Pregnancy outcome and the number of total and mature DCs was evaluated in the periphery and in the uterus. The effect of hCG on DC maturation and functionality was assessed in vitro. hCG and LH application totally prevented fetal rejection while P did not. The protective effect of hCG and LH was associated with a reduction in the number of total and mature DCs in the periphery and at the fetal maternal interface. By contrast, P did not affect DC phenotype. In vitro, hCG impaired the maturation process of DCs confirming our in vivo data. Our results highlights the importance of hormones in regulating the initiation of the adaptive immune response that allows the transient acceptance of paternal antigens and thus importantly contributes to pregnancy success.