Immunomodulation by Pregnancy Specific Glycoprotein 17

负责保护胎儿半同种异体移植物免受母体免疫系统攻击的机制是 复杂，并不完全理解。2型（TH 2）免疫应答的消失被认为是一种 “怀孕成功的关键因素以及孕妇疾病活动的减少， 患有某些自身免疫性疾病胎盘产生的激素和细胞因子与 TH 2环境的产生。妊娠特异性糖蛋白（PSG）由胎盘产生， 从着床时分泌到母体循环中。Abs对PSG的中和导致 结果表明，PSGs能诱导自然流产患者产生抗炎细胞因子， 可能在怀孕期间调节免疫反应中起重要作用。我们的长期目标是定义 PSG在正常和异常妊娠中的作用和机制。这个问题的核心假设是 本发明的应用是鼠PSG 17有助于建立有利于TH 2免疫应答的免疫环境。 反应拟议研究背后的基本原理是，更好地了解PSG在控制 怀孕期间的免疫可能导致对患有复发性乳腺癌的妇女实施新的疗法。 妊娠损失和其他免疫性疾病。为了实现本申请的目标，我们将 三个具体目标：（1）确定PSG 17-CD 9相互作用是否提供了共刺激信号， 幼稚CD 4 T细胞分化为CD 4效应T辅助细胞。这将通过确定是否 PSG 17与其受体CD 9的结合影响这些细胞的增殖和它们分泌的细胞因子。（二） 确定PSG 17与APC结合是否有利于抗原接触前后的TH 2细胞发育。为此 目的：探讨PSG 17对树突状细胞的作用及对APC的影响 在它们诱导源自TcR转基因小鼠的T细胞分化的能力方面， 刺激(3)确定非妊娠PSG 17表达小鼠对寄生虫的体内反应性质。小鼠 将用鼠鞭虫和肠系膜淋巴结中的细胞因子表达攻击注射了PSG 17的小鼠， 将分析总血清IG水平和蠕虫负荷。

The mechanisms responsible for the protection of the fetal semiallograft from attack by the matemal immune system are complex and remain incompletely understood. Establishemnt of a type-2 (TH2) immune response is believed to be one 'of the key factors responsible for pregnancy success as well as for the decreases in disease activity in pregnant women suffering from certain autoimmune diseases. Hormones and eytokines produced by the placenta have been implicated in the generation of the TH2 environment. Pregnancy specific glycoproteins (PSGs) are produced by the placenta and are secreted into the maternal circulation from the time of implantation. Neutralization of PSGs by Abs leads to spontaneous abortion and PSGs induce the secretion of anti-inflammatory cytokines.These findings suggest that PSGs may have an important role in regulation of the immune response during pregnancy. Our long-term goal is to define the roles and mechanisms of action of PSGs in normal and abnormal pregnancies. The central hypothesis of this application is that murine PSG 17 contributes to the establishment of an immune environment favoring a TH2 immune response. The rationale behind the proposed research is that a better understanding of the role of PSGs in controlling immunity during pregnancy could result in the implementation of new therapies for women suffering of recurrent pregnancy losses and other immune-based pathologies. To accomplish the objectives of this applieationwe will pursue three specific aims: (1) Determine whether PSG17-CD9 interactions provide a co-stimulatory signal that stimulates naive CD4 T cell differentiation to CD4 effector T helper cells. This will be accomplished by establishing whether binding of PSG17 to its receptor CD9 affects the proliferation of these cells and the cytokines they secrete. (2) Determine whether PSG17 binding to APC favors TH2 cell development before and after Ag encounter. For this purpose, we will evaluate the effects of P SG 17 treatment of dendritic cells and the effects of P SG 17 treatment in APC in their ability to induce differentiation of T cells derived from TcR transgenic mice upon primary and secondary stimulaton. (3) Determine the nature of the in vivo response of non-pregnant PSG17-expressing mice to a parasite. Mice injected with PSG17 will be challenged with Trichuris muris and the cytokine expression in mesenteric lymph nodes, total serum Ig levels and worm burden will be analyzed.