Research Institute of the McGill University Health Center, Glen Site, 1001 Décarie Boulevard, Block E, Rm EM3.3238, Montréal, Québec, H4A 3J1, Canada.
Division of Experimental Medicine, McGill University, Montréal, Québec, Canada.
BMC Immunol. 2019 Jan 29;20(1):8. doi: 10.1186/s12865-018-0272-x.
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.
自然杀伤细胞对病毒感染或转化细胞的反应依赖于通过抑制性和激活自然杀伤细胞受体接收信号的整合。人类白细胞抗原缺失细胞在体外用于通过缺失自我机制刺激自然杀伤细胞激活。另一方面，CEM.NKr.CCR5 细胞用于通过抗体依赖性方式刺激自然杀伤细胞，因为它们对自然杀伤细胞的直接杀伤具有抗性。K562 和 721.221 细胞系均缺乏抑制性自然杀伤细胞受体的表面主要组织相容性复合物 I 类配体。先前比较 K562 和 721.221 刺激自然杀伤细胞的工作发现，它们刺激了不同频率的自然杀伤细胞功能亚群。我们假设 K562、721.221 或 CEM.NKr.CCR5 刺激后的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 表达更高强度的自然杀伤细胞 G2D 配体和自然细胞毒性受体配体，这些配体参与触发自然杀伤细胞细胞毒性。721.221 细胞表达更多的激活自然杀伤细胞受体配体。721.221 表达 CD48、80 和 86，其平均荧光强度高于 K562。在 CEM.NKr.CCR5 细胞上以高强度检测到的唯一激活受体配体是 CD48 和细胞间粘附分子-2。
K562 表达的配体与自然杀伤细胞受体结合，诱导细胞溶解。这与 CD107a 功能对 K562 诱导的自然杀伤细胞功能的总贡献高于 721.221 细胞的贡献一致。721.221 细胞上表达的配体可以与更多数量的激活自然杀伤细胞受体结合，这可能解释了它们激活这些细胞成为功能细胞并分泌细胞因子的频率更大的原因。CEM.NKr.CCR5 上表达的少量激活自然杀伤细胞受体配体可能降低了它们以抗体非依赖性方式激活自然杀伤细胞的能力，这解释了它们相对抵抗直接自然杀伤细胞细胞毒性的原因。
