精浆参与雌性Treg细胞数量调节的机制及特点研究

项目名称： 精浆参与雌性Treg细胞数量调节的机制及特点研究

项目编号： No.81200479

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 医学二处

项目作者： 殷广洁

作者单位： 青岛大学

项目金额： 23万元

中文摘要： Treg（Tr)在正常妊娠母胎免疫耐受调节中发挥关键作用。研究显示，精浆可上调雌鼠生殖道局部Tr数量，下调MHC抗原特异的迟发超敏反应，其机制尚未阐明。我们推测精浆可能影响Tr新生、增殖或募集，并在Tr新生角度提出假说：精浆中TGF-β及精浆抗原共同作用，诱导CD4+CD25- T细胞向Tr转化，此过程需要APC参与；新生Tr以诱导生成的Tr(iTreg)为主，其介导免疫抑制具有MHC抗原特异性。故本研究拟⑴免疫磁珠分选Tr，体外观察精浆对Tr增殖的影响；⑵分选CD4+CD25- T细胞，将其与精浆、APC共培养，体外观察精浆诱导Tr新生及其机制；⑶利用输精管切除雄鼠交配模型，体内观察精浆接触后Tr数量调节及时间规律、Tr相关趋化因子的表达；⑷通过MLR抑制实验或Tr过继转输，体内和体外反复验证新生Tr的MHC抗原特异性。本研究将丰富母胎免疫耐受理论，并为相关疾病发病机制研究提供新的思路。

中文关键词： 母胎免疫耐受；精浆；调节性T细胞；；

英文摘要： Immune tolerance in pregnancy is the absence of a maternal immune response against the fetus and placenta, which thus may be viewed as unusually successful allografts, since they genetically differ from the mother.Many studies strongly support the notion that regulatory T（Treg）cells play a critical role in facilitating the maternofetal immune tolerance and mataining normal pregnancy. Previous study showed that seminal fluid(especially seminal plasma)exposure at mating could induce a temporary suppression of female reproductive immunity before the implantation of fetus, accompanied by a up-regulation of Foxp3+ T regulatory cell population in uterine and para-aortic lymph nodes in mice,however,the machanisms in this process has not been well described.In this study,we would like to determine which components in seminal plasma, immunosuppressive cytokines(TGF-β as an example) or kinds of antigens, were the key reason of up-regulation of Treg populations. Besides, we mean to identify if the sperm plasma could induce the generation of Tregs in a antigen-specific way. The achievements in this study may further the understanding of maternofetal immune tolerance .

英文关键词： Maternofetal immune tolerance；Seminal plasma；Treg cells；；