Blois Sandra M, Alba Soto Catalina D, Tometten Mareike, Klapp Burghard F, Margni Ricardo A, Arck Petra C
Charité, Department of Internal Medicine, Biomedizinisches Forschungszentrum, Campus Virchow, Humboldt University of Berlin, 13353 Berlin, Germany.
Biol Reprod. 2004 Apr;70(4):1018-23. doi: 10.1095/biolreprod.103.022640. Epub 2003 Dec 17.
Dendritic cells (DCs) are known to play a major role in the induction, maintenance, and regulation of immune responses. Recently, DCs have been described to be present at the feto-maternal interface in human decidua. However, only limited information is available about DC presence, phenotype, and--more importantly--function throughout gestation. Thus, we analyzed local (uterine) and systemic (blood) DCs in a murine model. DBA/2J mated CBA/J females with vaginal plugs were separated and killed on Gestation Days (GDs) 1.5, 3.5, 5.5, 6.5, 7.5, 8.5, 10.5, 13.5, 15.5, or 17.5. Frequency of uterine and blood CD11c+ DC, phenotype (coexpression of CD8alpha and major histocompatibility complex class II [MHC II] antigens), and presence of intracellular cytokines (interleukins 12 and 10) were determined by flow cytometry. The morphology of DC in the pregnant uterus was evaluated by immunohistochemistry. In uterus, the relative number of CD11c+ cells increased from GD 5.5, reaching a plateau on GD 9.5 until GD 17.5, while a transient peak of systemic CD11c+ cells was found on GD 8.5 and 10.5. The vast majority of uterine DCs were CD8alpha- and thus, belonged to the myeloid lineage. Interestingly, a significant peak of lymphoid DC was present on GD 1.5 and 5.5. Further, significantly more intracellular interleukin 10 than interleukin 12 was present in CD11c+ cells. Interestingly, mature DCs (MHC II+) were diminished from GD 5.5 to 8.5. Characterization of CD11c+ cell kinetics in uterus and blood reveals variation of phenotype during pregnancy, pointing toward an eminent immunoregulatory role of DCs throughout gestation at the feto-maternal interface.
已知树突状细胞(DCs)在免疫反应的诱导、维持和调节中起主要作用。最近,有人描述DCs存在于人类蜕膜的母胎界面处。然而,关于整个妊娠期DCs的存在、表型以及更重要的功能,目前仅有有限的信息。因此,我们在一个小鼠模型中分析了局部(子宫)和全身(血液)的DCs。将有阴道栓的DBA/2J与CBA/J雌性交配,然后在妊娠第1.5、3.5、5.5、6.5、7.5、8.5、10.5、13.5、15.5或17.5天处死。通过流式细胞术测定子宫和血液中CD11c⁺ DC的频率、表型(CD8α和主要组织相容性复合体II类[MHC II]抗原的共表达)以及细胞内细胞因子(白细胞介素12和10)的存在情况。通过免疫组织化学评估妊娠子宫中DC的形态。在子宫中,CD11c⁺细胞的相对数量从妊娠第5.5天开始增加,在妊娠第9.5天至17.5天达到平台期,而在妊娠第8.5天和10.5天发现全身CD11c⁺细胞出现短暂峰值。绝大多数子宫DCs为CD8α阴性,因此属于髓系谱系。有趣的是,在妊娠第1.5天和5.5天存在显著的淋巴样DC峰值。此外,CD11c⁺细胞中细胞内白细胞介素10的含量明显多于白细胞介素12。有趣的是,成熟DCs(MHC II⁺)从妊娠第5.5天至8.5天减少。子宫和血液中CD11c⁺细胞动力学的特征揭示了妊娠期表型的变化,表明DCs在整个妊娠期母胎界面处具有重要的免疫调节作用。