Target-effector interaction in the natural killer (NK) cell system. II. The isolation of NK cells and studies on the mechanism of killing.
Target-effector interaction in the natural killer (NK) cell system. II. The isolation of NK cells and studies on the mechanism of killing.
复制标题
自然杀伤 (NK) 细胞系统中的靶标-效应器相互作用。
作者：
J. Roder;R. Kiessling;P. Biberfeld;B. Andersson
我们以前已经表明，在正常小鼠中的尼龙毛非粘附淋巴样细胞的亚群选择性地结合到对自然杀伤（NK）细胞杀伤敏感的肿瘤细胞靶点。在本报告中，这些靶结合细胞（TBC）通过速度沉降富集或耗尽，并且单个靶-效应物缀合物的分离表明大多数TBC杀死其靶。此外，TBC的频率相关性以及（r = 0.86）在动力学实验过程中的人口裂解。TBC类似于小的静息淋巴细胞，其在靶细胞接触区域具有膜特化，如电子显微镜和细胞化学技术所示。在动力学研究中，靶细胞结合发生在裂解之前，并且与缺乏表面IG或θ-承载细胞的胰蛋白酶化群体的裂解潜力平行再生。在EDTA存在下防止细胞接触，而代谢抑制剂或丝氨酸蛋白酶抑制剂抑制裂解，对TBC的频率没有影响。相反，干扰素诱导剂升高NK介导的细胞溶解，对TBC水平没有影响。这些结果表明，i）我们检测到的大部分TBC代表NK细胞，并且ii）裂解和结合是独立控制的事件。提出了一种NK介导的细胞溶解的初步模型。
We have previously shown that a subpopulation of nylon wool nonadherent, lymphoid cells in normal mice binds selectively to tumor cell targets that are sensitive to killing by natural killer (NK) cells. In the present report these target-binding cells (TBC) were enriched or depleted by velocity sedimentation and the isolation of single target-effector conjugates indicated that the majority of TBC killed their targets. Furthermore, the frequency of TBC correlated well (r = 0.86) with lysis in a population during kinetics experiments. TBC resembled small, resting lymphocytes with membrane specializations in the area of target cell contact as indicated by electron microscopy and cytochemical techniques. Target cell binding occurred before lysis in kinetics studies and regenerated in parallel with the lytic potential of a trypsinized population devoid of surface Ig or θ-bearing cells. Cell contact was prevented in the presence of EDTA whereas metabolic inhibitors or inhibitors of serine proteases suppressed lysis with no effect on the frequency of TBC. Conversely, an interferon-inducing agent elevated NK-mediated cytolysis with no effect on the level of TBC. These results suggest that i) the majority of TBC that we detect represents the NK cell and ii) lysis and binding are independently controlled events. A tentative model of NK-mediated lysis is proposed.