Smithson G, Wolcott R M, Chervenak R
Department of Microbiology and Immunology, Louisiana State University Medical Center, Shreveport 71130.
Cancer Res. 1992 Aug 1;52(15):4149-56.
We have developed a model system which can be utilized for characterizing both the molecular basis of natural killer (NK):tumor interactions and the consequences of these interactions on tumor growth in vivo. This model system consists of several tumor lines which were derived from the murine lymphoma ASL1w under conditions which permitted the isolation of clonal lines that differ in their susceptibility to NK-mediated lysis. The NK-resistant clones used in this study (AW5J and AW5E) were susceptible to cytotoxic T-lymphocyte-mediated lysis and thus appear to be resistant to lytic processes utilized uniquely by NK cells. In competitive (cold target) inhibition assays, the AW5J clone did not inhibit NK recognition as well as the NK-sensitive clones. Thus AW5J may not be efficiently recognized by NK cells. The AW5E clone, on the other hand, competitively inhibited NK recognition as efficiently as the NK-sensitive clones; therefore, AW5E appears to evade a post-recognition event which is required for NK-mediated lysis. The susceptibility of these clones to killing by NK cells directly correlated with their lethality, suggesting that NK cells regulated the growth of these tumors in vivo. The level of host NK activity was also an important determinant of the level and site of tumor localization. Two-step immunofluorescence assays and flow cytometric analysis were used to quantitate the number of tumor cells in the bone marrow, spleen, and lymph nodes of mice with augmented or depleted NK activity. Increasing host NK activity decreased the number of tumor cells in each organ which could support the growth of the particular tumor tested. Furthermore, the extent of NK regulation was dependent, in part, upon the susceptibility of the particular tumor to NK-mediated lysis and the site of tumor growth. Thus, the data presented here demonstrate the utility of the ASL1w-derived clones as a model system which can be used to delineate the requirements and consequences of NK:tumor interactions.
我们开发了一种模型系统，可用于表征自然杀伤（NK）细胞与肿瘤相互作用的分子基础以及这些相互作用对体内肿瘤生长的影响。该模型系统由几个肿瘤细胞系组成，这些细胞系源自鼠淋巴瘤ASL1w，其培养条件允许分离出对NK介导的裂解敏感性不同的克隆细胞系。本研究中使用的NK抗性克隆（AW5J和AW5E）对细胞毒性T淋巴细胞介导的裂解敏感，因此似乎对NK细胞特有的裂解过程具有抗性。在竞争性（冷靶）抑制试验中，AW5J克隆对NK识别的抑制作用不如NK敏感克隆。因此，AW5J可能不能被NK细胞有效识别。另一方面，AW5E克隆与NK敏感克隆一样有效地竞争性抑制NK识别；因此，AW5E似乎逃避了NK介导的裂解所需的识别后事件。这些克隆对NK细胞杀伤的敏感性与其致死率直接相关，表明NK细胞在体内调节这些肿瘤的生长。宿主NK活性水平也是肿瘤定位水平和部位的重要决定因素。采用两步免疫荧光测定法和流式细胞术分析来定量NK活性增强或降低的小鼠骨髓、脾脏和淋巴结中的肿瘤细胞数量。增加宿主NK活性可减少每个器官中能够支持所测试特定肿瘤生长的肿瘤细胞数量。此外，NK调节的程度部分取决于特定肿瘤对NK介导的裂解的敏感性以及肿瘤生长部位。因此，本文提供的数据证明了源自ASL1w的克隆作为一种模型系统的实用性，该系统可用于描述NK细胞与肿瘤相互作用的要求和后果。
