Collins J L, Patek P Q, Cohn M
J Exp Med. 1981 Jan 1;153(1):89-106. doi: 10.1084/jem.153.1.89.
Detailed analysis of the natural killer (NK) activity directed at nontumorigenic cell lines and their transformed tumorigenic derivatives has revealed a paradox. On the one hand, a correlation has been found between the tumorigenic potential of chemically transformed fibroblast cell lines and their sensitivity to NK cells in vitro. Nontransformed cells (N-type cell lines) and cells tumorigenic in normal mice (C-type cell lines) are resistant to NK-mediated lysis. In contrast, cell lines that are tumorigenic in ATxFL mice (these mice are very low in NK activity), but not in normal mice (I-type cell lines) are sensitive to NK-mediated lysis. These findings support the concept that NK activity is involved in host surveillance against tumors. On the other hand, NK-resistant fibroblasts, whether taken directly form animals or derived as tumorigenic or nontumorigenic cell lines, compete with NK-sensitive target cells to inhibit their lysis by NK effectors. Not only are both NK-sensitive and -resistant cells recognized by NK effectors but both receive lytic signals from NK effector cells. Target cell resistance is a result of a protein synthesis-dependent mechanism that prevents lysis such that in the presence of inhibitors of protein synthesis all fibroblasts tested are NK sensitive. Those fibroblasts that are normally sensitive to NK-mediated lysis must be deficient in their ability to produce or respond to this counterlytic mechanism. These findings are in contrast with the general findings when lymphoid cells are studied as NK targets where sensitivity appears to be a result of recognition by NK effectors. Because our findings show that transformed and normal cells express the same recognition determinants, in order for NK activity to play an important in vivo role in tumor surveillance, a mechanism must operate to permit NK effectors to find their targets in vivo. In the absence of a special discrimination mechanism, the killing of NK-sensitive transformants that arise autochronously would be less than optimal as a consequence of competition by the normal, NK-resistant, cells.
对针对非致瘤细胞系及其转化的致瘤衍生物的自然杀伤（NK）活性进行的详细分析揭示了一个矛盾现象。一方面，已发现化学转化的成纤维细胞系的致瘤潜力与其在体外对NK细胞的敏感性之间存在相关性。未转化的细胞（N型细胞系）和在正常小鼠中具有致瘤性的细胞（C型细胞系）对NK介导的裂解具有抗性。相比之下，在ATxFL小鼠（这些小鼠的NK活性非常低）中具有致瘤性但在正常小鼠中不具有致瘤性的细胞系（I型细胞系）对NK介导的裂解敏感。这些发现支持了NK活性参与宿主对肿瘤的监视这一概念。另一方面，NK抗性成纤维细胞，无论是直接从动物获取还是作为致瘤或非致瘤细胞系衍生而来，都与NK敏感靶细胞竞争，以抑制它们被NK效应细胞裂解。NK效应细胞不仅能识别NK敏感和抗性细胞，而且两者都能从NK效应细胞接收裂解信号。靶细胞抗性是一种依赖蛋白质合成的机制的结果，该机制可防止裂解，因此在存在蛋白质合成抑制剂的情况下，所有测试的成纤维细胞对NK都是敏感的。那些通常对NK介导的裂解敏感的成纤维细胞在产生或响应这种抗裂解机制的能力方面必定存在缺陷。这些发现与将淋巴细胞作为NK靶标进行研究时的一般发现形成对比，在后者中，敏感性似乎是NK效应细胞识别的结果。因为我们的发现表明转化细胞和正常细胞表达相同的识别决定簇，为了使NK活性在体内肿瘤监视中发挥重要作用，必须有一种机制来使NK效应细胞在体内找到它们的靶标。在没有特殊识别机制的情况下，由于正常的NK抗性细胞的竞争，自发产生的NK敏感转化体的杀伤效果将不尽人意。
