本文關鍵詞：體外誘導的妊娠不同時期胎盤源性樹突狀細胞生物學特性的初步研究　出處：《南京醫(yī)科大學》2007年碩士論文　論文類型：學位論文

  更多相關文章： 妊娠 胎盤 單核-巨噬細胞 內(nèi)皮(逆)穿越 樹突狀細胞 生物學特性

【摘要】： 樹突狀細胞(Dendritic cells，DCs)作為免疫應答的調(diào)控細胞，在免疫激活以及免疫耐受中的作用越來越受到眾人的矚目。近年來的研究表明，在母胎接觸面存在著DCs，，并且可能參與了正常妊娠時對胎兒抗原的免疫耐受以及分娩的發(fā)動。但是其確切的機制目前仍不明了。為此，本研究首先參照單核-巨噬細胞在體內(nèi)經(jīng)歷組織淋巴遷移發(fā)育分化成樹突狀細胞的過程，建立了三維的肉皮單層培養(yǎng)體系，然后分別將中期妊娠胎盤和足月胎盤來源的單核-巨噬細胞加入其中，憑借單核-巨噬細胞的遷移本性，正、反兩次穿越內(nèi)皮單層，使其分化發(fā)育成兩種不同的DCs。這一模型系統(tǒng)模擬了體內(nèi)單核-巨噬細胞在移動中分化發(fā)育為樹突狀細胞的過程。然后，我們對這兩種DCs的表型、功能以及生物學特性進行比較，觀察不同妊娠階段胎盤源性DCs表型和功能上的差異，并據(jù)此分析胎盤DCs在妊娠耐受和分娩發(fā)動中的可能作用。 結果表明足月胎盤來源的單核-巨噬細胞經(jīng)過內(nèi)皮單層誘導培養(yǎng)48h后，在內(nèi)皮上方再現(xiàn)的細胞具有明顯的樹突狀形態(tài)，高表達白細胞抗原CD45以及共刺激分子CD80、CD86和MHC-Ⅱ類分子HLA-DR，并具有較強的刺激同源異體淋巴細胞增殖的能力。對其生物學特性的研究表明，該種DCs表面低表達Fas-L，不分泌IL-12P40和IL-10，可以誘導與之相作用的淋巴細胞更多的表達Th1型細胞因子IFN-γ。相比較而言，中期妊娠胎盤來源的單核-巨噬細胞經(jīng)過內(nèi)皮單層誘導培養(yǎng)48h后，在內(nèi)皮上方再現(xiàn)的細胞則低表達共刺激分子CD80和CD86，尤其低表達共刺激分子CD80，具有較弱的刺激同源異體淋巴細胞增殖的能力；分泌細胞因子亦與晚期妊娠胎盤來源的DCs有所不同，表現(xiàn)在中期妊娠胎盤來源的DCs分泌IL-10，但是同樣不分泌IL-12；可以誘導與之相作用的淋巴細胞形成較多的IL-10分泌細胞，而Th1型細胞因子IFN-γ的分泌細胞水平則較低。據(jù)此我們認為胎盤源性的單核-巨噬細胞可以在內(nèi)皮(逆)穿越模型中分化為樹突狀細胞，并且處于妊娠不同階段的單核-巨噬細胞可能分化為功能不同的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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