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Expression of ligands for activating natural killer cell receptors on cell lines commonly used to assess natural killer cell function
BMC Immunology ( IF 3 ) Pub Date : 2019-01-29 , DOI: 10.1186/s12865-018-0272-x
Alexandra Tremblay-McLean , Sita Coenraads , Zahra Kiani , Franck P. Dupuy , Nicole F. Bernard

Natural killer cell responses to virally-infected or transformed cells depend on the integration of signals received through inhibitory and activating natural killer cell receptors. Human Leukocyte Antigen null cells are used in vitro to stimulate natural killer cell activation through missing-self mechanisms. On the other hand, CEM.NKr.CCR5 cells are used to stimulate natural killer cells in an antibody dependent manner since they are resistant to direct killing by natural killer cells. Both K562 and 721.221 cell lines lack surface major histocompatibility compatibility complex class Ia ligands for inhibitory natural killer cell receptors. Previous work comparing natural killer cell stimulation by K562 and 721.221 found that they stimulated different frequencies of natural killer cell functional subsets. We hypothesized that natural killer cell function following K562, 721.221 or CEM.NKr.CCR5 stimulation reflected differences in the expression of ligands for activating natural killer cell receptors. K562 expressed a higher intensity of ligands for Natural Killer G2D and the Natural Cytotoxicity Receptors, which are implicated in triggering natural killer cell cytotoxicity. 721.221 cells expressed a greater number of ligands for activating natural killer cell receptors. 721.221 expressed cluster of differentiation 48, 80 and 86 with a higher mean fluorescence intensity than did K562. The only ligands for activating receptor that were detected on CEM.NKr.CCR5 cells at a high intensity were cluster of differentiation 48, and intercellular adhesion molecule-2. The ligands expressed by K562 engage natural killer cell receptors that induce cytolysis. This is consistent with the elevated contribution that the cluster of differentiation 107a function makes to total K562 induced natural killer cell functionality compared to 721.221 cells. The ligands expressed on 721.221 cells can engage a larger number of activating natural killer cell receptors, which may explain their ability to activate a larger frequency of these cells to become functional and secrete cytokines. The few ligands for activating natural killer cell receptors expressed by CEM.NKr.CCR5 may reduce their ability to activate natural killer cells in an antibody independent manner explaining their relative resistance to direct natural killer cell cytotoxicity.

中文翻译:

用于活化自然杀伤细胞受体的配体在通常用于评估自然杀伤细胞功能的细胞系上的表达

对病毒感染或转化的细胞的自然杀伤细胞反应取决于通过抑制和激活自然杀伤细胞受体接收到的信号的整合。人类白细胞抗原无效细胞可用于体外,通过失踪自我机制刺激自然杀伤细胞的激活。另一方面,CEM.NKr.CCR5细胞以抗体依赖性方式用于刺激自然杀伤细胞,因为它们对自然杀伤细胞的直接杀伤具有抵抗力。K562和721.221细胞系均缺乏用于抑制自然杀伤细胞受体的表面主要组织相容性相容性Ia类配体。先前的工作比较了K562和721.221对自然杀伤细胞的刺激,发现它们刺激了不同频率的自然杀伤细胞功能子集。我们假设K562、721.221或CEM.NKr.CCR5刺激后自然杀伤细胞功能反映了激活自然杀伤细胞受体的配体表达的差异。K562表达了天然杀伤剂G2D和天然细胞毒性受体的配体强度更高,这与触发天然杀伤细胞的细胞毒性有关。721.221细胞表达了更多的激活天然杀伤细胞受体的配体。721.221表达分化簇48、80和86,其平均荧光强度高于K562。在CEM.NKr.CCR5细胞上高强度检测到的唯一激活受体的配体是分化簇48和细胞间粘附分子2。K562表达的配体与诱导细胞溶解的自然杀伤细胞受体结合。与721.221细胞相比,分化107a功能簇对总的K562诱导的自然杀伤细胞功能的增加贡献是一致的。在721.221细胞上表达的配体可以与大量活化的自然杀伤细胞受体结合,这可能解释了它们活化较大频率的这些细胞成为功能并分泌细胞因子的能力。CEM.NKr.CCR5表达的少数几种激活自然杀伤细胞受体的配体可能会以不依赖抗体的方式降低其激活自然杀伤细胞的能力,这说明了它们对直接自然杀伤细胞的细胞毒性的相对抵抗力。221个单元格。在721.221细胞上表达的配体可以与大量活化的自然杀伤细胞受体结合,这可能解释了它们活化较大频率的这些细胞成为功能并分泌细胞因子的能力。CEM.NKr.CCR5表达的少数几种激活自然杀伤细胞受体的配体可能会以不依赖抗体的方式降低其激活自然杀伤细胞的能力,这说明了它们对直接自然杀伤细胞的细胞毒性的相对抵抗力。221个单元格。在721.221细胞上表达的配体可以与大量活化的自然杀伤细胞受体结合,这可能解释了它们活化较大频率的这些细胞成为功能并分泌细胞因子的能力。CEM.NKr.CCR5表达的少数几种激活自然杀伤细胞受体的配体可能会以不依赖抗体的方式降低其激活自然杀伤细胞的能力,这说明了它们对直接自然杀伤细胞的细胞毒性的相对抵抗力。
更新日期:2019-01-29
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