Characterization of natural killer cells in nonobese diabetic/severely compromised immunodeficient mice during pregnancy
Characterization of natural killer cells in nonobese diabetic/severely compromised immunodeficient mice during pregnancy
复制标题
妊娠期间非肥胖糖尿病/严重免疫缺陷小鼠自然杀伤细胞的特征。
DOI：
10.1016/j.fertnstert.2007.08.087
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发表时间：
2009-06-01
影响因子：
6.7
通讯作者：
Zeng, Shan
中科院分区：
文献类型：
--
作者：
Lin, Yi;Zhong, Yanmin;Zeng, Shan
目的：描述非肥胖糖尿病/严重免疫缺陷患者的子宫自然杀伤（uNK）细胞特征，（NOD/SCID）小鼠，并研究这些细胞在妊娠耐受中的潜在作用。设计：基于动物模型的研究。设置：大学的学术研究中心。动物：将同基因妊娠NOD/SCID小鼠与非免疫缺陷BALB/c小鼠进行比较。干预：Toll样受体（TLR）激动剂的诱导。主要结果测量：进行流式细胞术分析以检测细胞亚群的百分比，并进行标准Cr-51释放试验以确定细胞毒性。结果：NOD/SCID小鼠中uNK细胞的主要亚群是DX 5（CD 49 b）（+）、脱唾液酸神经节-N-四糖基酰胺（+）、CD 25（+）、CD 122（+）、Thy-1（CD 90）（hi）、c-kit（CD 117）（hi）和白细胞介素-10（+）。此外，在NOD/SCID小鼠中，干扰素-γ（+）亚群的百分比响应于选定的TLR激动剂而略微增加，而在BALB/c小鼠中相应的百分比可以显著增加。这种作用可以被抑制剂消除，包括LY 294002、SP 600125和PD 98059。BALB/c小鼠IFN-γ（+）NK细胞百分率的显著增加伴随着胚胎吸收率的增加。与此相反，NOD/SCID小鼠的吸收率没有显着增加后，诱导的聚肌胞苷酸或脂多糖。正如所预期的，来自NOD/SCID小鼠的NK细胞显示出可检测的但低于BALB/c的细胞毒性，如通过标准Cr-51释放测定所确定的。此外，NOD/SCID小鼠的uNK细胞对脂多糖诱导的诱生型一氧化氮合酶（inducible nitric oxide synthesis. Conclusions）也表现出低敏感性。这些细胞对所选TLR激动剂的刺激低敏感。这种状态似乎有利于维持妊娠。（Fertil Steril（R）2009;91：2676-86.（C）2009年由美国生殖医学协会。
Objective: To characterize uterine natural killer (uNK) cells in nonobese diabetic/severely compromised immunodeficient (NOD/SCID) mice and investigate the potential role of these cells in pregnancy tolerance.Design: An animal model-based study.Setting: Academic research center in a university.Animal(s): Syngeneic pregnant NOD/SCID mice were compared with non-immunodeficient BALB/c mice.Intervention(s): Induction of Toll-like receptor (TLR) agoinsts.Main Outcome Measure(s): Flow cytometric analysis was performed to detect the percentage of cell subsets, and standard Cr-51 release assay was performed to determine cytotoxicity.Result(s): The dominant subset of uNK cells in NOD/SCID mice is DX5 (CD49b)(+), asialo ganglio-N-tetraosyleeramide(+), CD25(+), CD122(+), Thy-1 (CD90)(hi), c-kit (CD117)(hi), and interleukin-10(+). In addition, the percentage of interferon-gamma(+) subset was slightly increased in response to selected TLR agonists in the NOD/SCID mice, whereas the corresponding percentage in BALB/c mice could be increased dramatically. Such an effect could be abrogated by inhibitors, including LY294002, SP600125, and PD98059. The significant increase of interferon-gamma(+) NK cell percentage in BALB/c mice was concomitant with the increase of the embryo resorption rate. In contrast, the resorption rate in NOD/SCID mice was not significantly increased upon the induction of polyinosinic polycytidylic acid or lipopolysaccharide. As expected, the NK cells from NOD/SCID mice display a detectable but lower cytotoxicity than BALB/c, as determined by standard Cr-51 release assay. In addition, the uNK cells from NOD/SCID mice also display a hyposensitivity to lipopolysaccharide-induced production of inducible nitric oxide synthase.Conclusion(s): A considerable percentage of immature NK cells were detected at the fetomaternal interface in NOD/SCID mice. These cells were hyposensitive to the stimulation of selected TLR agonists. Such a status seemed to be beneficial for the maintenance of pregnancy. (Fertil Steril (R) 2009;91:2676-86. (C)2009 by American Society for Reproductive Medicine.)