Natural killer cells kill tumour cells at a given stage of differentiation
Natural killer cells kill tumour cells at a given stage of differentiation
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自然杀伤细胞在特定的分化阶段杀死肿瘤细胞
作者：
M. Gidlund;A. Örn;P. Pattengale;M. Jansson;H. Wigzell;K. Nilsson
自然杀伤（NK）细胞具有独特的表面特征和生理特性，并具有选择性溶解某些靶细胞而非其他靶细胞的能力1，2。然而，这种选择性的基础在效应细胞和靶细胞水平上仍然不清楚。提出的特异性NK细胞靶部分3 -5包括糖脂和与主要组织相容性复合体无关的糖蛋白，而恶性细胞和某些正常细胞已被发现对NK细胞介导的细胞溶解敏感6 -8。有充分的证据表明，NK细胞可以抑制体内少量移植肿瘤细胞的生长9，10，并可以限制继发性转移的建立11，12。因此，据推测，NK细胞作为一种原始的、胸腺非依赖性免疫系统发挥作用，使用遗传学上保留的靶结构形成细胞介导的抵抗某些肿瘤细胞生长的抗性屏障1。在新生小鼠和人类的胸腺8、13以及人类胎儿的骨髓中，存在对NK细胞非常敏感的明显正常的细胞，这表明NK细胞在其分化的特定阶段可能具有增加的导致细胞溶解的能力。与这一概念一致，处于不同分化阶段的胚胎癌细胞对NK细胞诱导的裂解显示出显著不同的易感性14。在这里，只有代表早期阶段的细胞类型对NK细胞介导的细胞溶解敏感，而分化程度更高的内胚层细胞系显示出接近完全抗性。因此，上述数据将支持这样的观点，即在体内，取决于分化阶段，正常细胞和恶性细胞都受到NK细胞的监视。在这里，我们已经考虑了分化相关的NK细胞的敏感性的问题，使用已知的细胞系进行控制分化的存在下，各种代理。三种肿瘤细胞系进行了研究，并都表现出显着的正相关性之间的减少NK细胞的敏感性和诱导分化的各种诱导剂。我们的研究结果支持了这样的观点，即对NK细胞介导的裂解的易感性可能根据靶细胞的分化阶段而变化。
Natural killer (NK) cells have unique surface features and physiological characteristics and a selective ability to lyse some, but not other, target cells1,2. However, the basis of this selectivity remains obscure at both effector and target cell levels. Proposed specific NK-cell target moieties3–5 include glycolipids, and glycoproteins unrelated to the major histocompatibility complex, while malignant and certain normal cells have been found to be susceptible to NK-cell-mediated cytolysis6–8. There is good evidence that NK cells can inhibit the outgrowth of small numbers of transplanted tumour cells in vivo9,10 and can restrict the establishment of secondary metastasis11,12. It has thus been speculated that NK cells function as a primitive, thymus-independent immune system using phylogenetically preserved target structures to form a cell-mediated resistance barrier against the outgrowth of certain tumour cells1. The presence in the thymuses of neonatal mice and humans8,13 and in the marrow of human fetuses, of apparently normal cells which are quite sensitive to NK cells suggested that NK cells might have an increased ability to cause the lysis of cells at a particular stage of their differentiation. In agreement with this concept, embryonal carcinoma cells at various stages of differentiation display a strikingly different susceptibility to NK-cell-induced lysis14. Here only cell types representing early stages were sensitive to NK-cell-mediated cytolysis, whereas the more differentiated endodermal cell lines showed close to complete resistance. The above data would thus support the view that, in vivo, depending on the stage of differentiation, both normal and malignant cells are under surveillance by NK cells. Here we have considered the question of differentiation-related NK-cell susceptibility using defined cell lines known to undergo controlled differentiation in the presence of various agents. Three tumour cell-lines were investigated, and all demonstrated a striking positive correlation between a decrease in NK-cell susceptibility and the induction of differentiation by the various inducers. Our findings support the view that susceptibility to NK-cell mediated lysis may vary according to the stage of differentiation of the target cell.