Department of Biological Engineering, Massachusetts Institute of Technology, 77 Massachusetts Ave., Cambridge, MA 02139, USA.
Integr Biol (Camb). 2012 Oct;4(10):1175-84. doi: 10.1039/c2ib20167d.
Natural killer (NK) cells are a subset of innate immune lymphocytes that interrogate potential target cells and rapidly respond by lysing them or secreting inflammatory immunomodulators. Productive interactions between NK cells and targets such as tumor cells or virally infected cells are critical for immunological control of malignancies and infections. For individual NK cells, however, the relationship between the characteristics of these cell-cell interactions, cytolysis, and secretory activity is not well understood. Here, we used arrays of subnanoliter wells (nanowells) to monitor individual NK cell-target cell interactions and quantify the resulting cytolytic and secretory responses. We show that NK cells operate independently when lysing a single target cell and that lysis is most probable during an NK cell's first encounter with a target. Furthermore, we demonstrate that the secretion of interferon-γ (IFN-γ) occurs most often among NK cells that become the least motile upon contacting a target cell but is largely independent of cytolysis. Our findings demonstrate that integrated analysis of the cell-cell interaction parameters, cytolytic activity, and secretory activity of single NK cells can reveal new insights into how these complex functions are related within individual cells.
自然杀伤 (NK) 细胞是先天免疫淋巴细胞的一个亚群，它们可以检测潜在的靶细胞，并通过溶解它们或分泌炎症免疫调节剂来迅速做出反应。NK 细胞与肿瘤细胞或病毒感染细胞等靶细胞之间的有效相互作用对于恶性肿瘤和感染的免疫控制至关重要。然而，对于单个 NK 细胞而言，这些细胞-细胞相互作用、细胞溶解和分泌活性的特征之间的关系尚不清楚。在这里，我们使用亚纳升级的纳米孔阵列（nanowell）来监测单个 NK 细胞-靶细胞相互作用，并定量分析由此产生的细胞溶解和分泌反应。我们发现 NK 细胞在裂解单个靶细胞时独立运作，并且在 NK 细胞与靶细胞的首次接触中最有可能发生细胞溶解。此外，我们证明 IFN-γ（干扰素-γ）的分泌最常发生在与靶细胞接触后变得最不活跃的 NK 细胞中，但在很大程度上与细胞溶解无关。我们的研究结果表明，对单个 NK 细胞的细胞-细胞相互作用参数、细胞溶解活性和分泌活性进行综合分析，可以揭示这些复杂功能在单个细胞内的关系的新见解。
