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当与白细胞介素-15、白细胞介素-18 和滋养层细胞共培养时,NK-92 细胞的表型和功能会发生变化。

NK-92 cells change their phenotype and function when cocultured with IL-15, IL-18 and trophoblast cells.

机构信息

Department of Immunology and Intercellular Interactions, Federal State Budgetary Scientific Institution, Research Institute of Obstetrics, Gynecology, and Reproductology named after D.O. Ott, Russia.

Department of Obstetrics, Federal State Budgetary Scientific Institution, Research Institute of Obstetrics, Gynecology, and Reproductology named after D.O. Ott, Russia.

出版信息

Immunobiology. 2021 Sep;226(5):152125. doi: 10.1016/j.imbio.2021.152125. Epub 2021 Jul 26.

DOI:10.1016/j.imbio.2021.152125
PMID:34365089
Abstract

NK cell development is affected by their cellular microenvironment and cytokines, including IL-15 and IL-18. NK cells can differentiate in secondary lymphoid organs, liver and within the uterus in close contact with trophoblast cells. The aim was to evaluate changes in the NK cell phenotype and function in the presence of IL-15, IL-18 and JEG-3, a trophoblast cell line. When cocultured with JEG-3 cells, IL-15 caused an increase in the number of NKG2D+ NK-92 cells and the intensity of CD127 expression. IL-18 stimulates an increase in the amount of NKp44+ NK-92 cells and in the intensity of NKp44 expression by pNK in the presence of trophoblast cells. NK-92 cell cytotoxic activity against JEG-3 cells increased only in presence of IL-18. Data on changes in the cytotoxic activity of NK-92 cells against JEG-3 cells in the presence of IL-15 and IL-18 indicate the modulation of NK cell function both by the cytokine microenvironment and directly by target cells. IL-15 and IL-18 were present in conditioned media (CM) from 1st and 3rd trimester placentas. In the presence of 1st trimester CM and JEG-3 cells, NK-92 cells showed an increase in the intensity of NKG2D expression. In the presence of 3rd trimester CM and JEG-3 cells, a decrease in the expression of NKG2D by NK-92 cells was observed. Thus, culturing of NK-92 cells with JEG-3 trophoblast cells stimulated a pronounced change in the NK cell phenotype, bringing it closer to the decidual NK cell-like phenotype.

摘要

自然杀伤 (NK) 细胞的发育受细胞微环境和细胞因子的影响,包括白细胞介素-15 (IL-15) 和白细胞介素-18 (IL-18)。NK 细胞可以在次级淋巴器官、肝脏和与滋养层细胞密切接触的子宫内分化。本研究旨在评估在白细胞介素-15 (IL-15)、白细胞介素-18 (IL-18) 和滋养层细胞系 JEG-3 的存在下,NK 细胞表型和功能的变化。当与 JEG-3 细胞共培养时,IL-15 导致 NKG2D+NK-92 细胞数量增加和 CD127 表达强度增加。在滋养层细胞存在的情况下,IL-18 刺激 NKp44+NK-92 细胞数量增加和 pNK 中 NKp44 表达强度增加。只有在存在白细胞介素-18 的情况下,NK-92 细胞对 JEG-3 细胞的细胞毒性活性才会增加。在白细胞介素-15 和白细胞介素-18 存在的情况下,NK-92 细胞对 JEG-3 细胞的细胞毒性活性的变化数据表明,NK 细胞功能既受到细胞因子微环境的调节,也受到靶细胞的直接调节。白细胞介素-15 和白细胞介素-18 存在于第一和第三孕期胎盘的条件培养基 (CM) 中。在第一孕期 CM 和 JEG-3 细胞存在的情况下,NK-92 细胞的 NKG2D 表达强度增加。在第三孕期 CM 和 JEG-3 细胞存在的情况下,NK-92 细胞的 NKG2D 表达减少。因此,用 JEG-3 滋养层细胞培养 NK-92 细胞刺激 NK 细胞表型发生明显变化,使其更接近蜕膜 NK 细胞样表型。

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