体外诱导的妊娠不同时期胎盘源性树突状细胞生物学特性的初步研究

发布时间：2018-01-08 14:17

  本文关键词：体外诱导的妊娠不同时期胎盘源性树突状细胞生物学特性的初步研究　出处：《南京医科大学》2007年硕士论文　论文类型：学位论文

  更多相关文章： 妊娠 胎盘 单核-巨噬细胞 内皮(逆)穿越 树突状细胞 生物学特性

【摘要】： 树突状细胞(Dendritic cells，DCs)作为免疫应答的调控细胞，在免疫激活以及免疫耐受中的作用越来越受到众人的瞩目。近年来的研究表明，在母胎接触面存在着DCs，，并且可能参与了正常妊娠时对胎儿抗原的免疫耐受以及分娩的发动。但是其确切的机制目前仍不明了。为此，本研究首先参照单核-巨噬细胞在体内经历组织淋巴迁移发育分化成树突状细胞的过程，建立了三维的肉皮单层培养体系，然后分别将中期妊娠胎盘和足月胎盘来源的单核-巨噬细胞加入其中，凭借单核-巨噬细胞的迁移本性，正、反两次穿越内皮单层，使其分化发育成两种不同的DCs。这一模型系统模拟了体内单核-巨噬细胞在移动中分化发育为树突状细胞的过程。然后，我们对这两种DCs的表型、功能以及生物学特性进行比较，观察不同妊娠阶段胎盘源性DCs表型和功能上的差异，并据此分析胎盘DCs在妊娠耐受和分娩发动中的可能作用。 结果表明足月胎盘来源的单核-巨噬细胞经过内皮单层诱导培养48h后，在内皮上方再现的细胞具有明显的树突状形态，高表达白细胞抗原CD45以及共刺激分子CD80、CD86和MHC-Ⅱ类分子HLA-DR，并具有较强的刺激同源异体淋巴细胞增殖的能力。对其生物学特性的研究表明，该种DCs表面低表达Fas-L，不分泌IL-12P40和IL-10，可以诱导与之相作用的淋巴细胞更多的表达Th1型细胞因子IFN-γ。相比较而言，中期妊娠胎盘来源的单核-巨噬细胞经过内皮单层诱导培养48h后，在内皮上方再现的细胞则低表达共刺激分子CD80和CD86，尤其低表达共刺激分子CD80，具有较弱的刺激同源异体淋巴细胞增殖的能力；分泌细胞因子亦与晚期妊娠胎盘来源的DCs有所不同，表现在中期妊娠胎盘来源的DCs分泌IL-10，但是同样不分泌IL-12；可以诱导与之相作用的淋巴细胞形成较多的IL-10分泌细胞，而Th1型细胞因子IFN-γ的分泌细胞水平则较低。据此我们认为胎盘源性的单核-巨噬细胞可以在内皮(逆)穿越模型中分化为树突状细胞，并且处于妊娠不同阶段的单核-巨噬细胞可能分化为功能不同的DCs。
[Abstract]:Dendritic cells (DC) act as regulatory cells for immune response. More and more attention has been paid to the role of immune activation and immune tolerance. Recent studies have shown that there is DCs on the maternal and fetal interface. And it may be involved in the immune tolerance to fetal antigens and the initiation of labor in normal pregnancy, but the exact mechanism is still unclear. Firstly, according to the process of monocyte-macrophage migration and differentiation into dendritic cells in vivo, a three-dimensional monocytoid monolayer culture system was established. Then the monocyte-macrophages from the placenta of second trimester and the placenta of term were added into the monocyte-macrophages respectively. By virtue of the migration nature of monocyte-macrophages, the mononuclear macrophages crossed the endothelial monolayer two times. The model system simulates the process of monocyte-macrophage differentiation into dendritic cells during migration. Then we study the phenotypes of these two DCs. Functional and biological characteristics were compared to observe the phenotypic and functional differences of placental DCs in different pregnancy stages and to analyze the possible role of placental DCs in pregnancy tolerance and labor initiation. The results showed that the mononuclear macrophages derived from the full-term placenta had dendritic morphology in the above endothelial cells after 48 hours of endothelial monolayer induction and culture. High expression of leukocyte antigen CD45, costimulatory molecules CD80, CD86 and MHC- 鈪

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