Whyte A L, Miller S C
Department of Anatomy and Cell Biology, McGill University, Montreal, Quebec, Canada.
Immunobiology. 1998 Jul;199(1):23-38. doi: 10.1016/S0171-2985(98)80061-2.
Natural killer (NK) cells are well established as fundamental elements in the early eradication of aberrant cells potentially leading to neoplasia. Moreover, it has also long been known that inbred strains of laboratory mice, as well as human individuals, demonstrate a wide range of NK cell-mediated immune response even to the same tumor. In the present study, various parameters which could lead ultimately to high, or low, NK cell-mediated functional activity have been assessed. Mice of the A/J strain demonstrate very low NK cell tumor-lytic activity and correspondingly high incidence of lymphoma. By contrast, C57B1/6 mice demonstrate relatively high NK cell activity and virtually never develop lymphomas. The results of this study have revealed that the absolute numbers of splenic NK cells were significantly lower in A/J vs C57B16/mice. Furthermore, the blood of A/J mice contained significantly fewer (30%) NK cells than did that of C57B1/6 mice. However, no significant difference between the 2 strains was found in the numbers of lymphocytic cells from NK cell-enriched fractions from the spleens, which possessed either the homing receptor MEL-14, or the integrin Mac-I, both essential surface molecules for transendothelial migration of lymphocytic cells from the circulation into organ parenchyma. Moreover, NK cells from both strains responded similarly to the NK cell stimulants, ATRA, indomethacin and interleukin-2. Finally, there was no significant difference between the 2 strains, in the numbers of lymphocytic cells in the bone marrow (including NK cells), which were radiolabelled with the DNA synthetic precursor, 3H-thymidine, indicative, thus, of equivalent levels of lymphocyte production by the bone marrow in the 2 strains. The observations collectively suggest that the low peripheral (spleen, blood) levels of NK cell-mediated functional activity found in the A/J strain of mouse at least, reflects either post-production, large-scale NK cell abortion/death, or a bone marrow-based microenvironmental deficiency which inhibits NK cells' exit from the bone marrow birth site.
自然杀伤（NK）细胞作为早期根除可能导致肿瘤形成的异常细胞的基本要素，已得到充分证实。此外，长期以来人们也知道，实验室小鼠的近交系以及人类个体，即使对同一肿瘤，也表现出广泛的NK细胞介导的免疫反应。在本研究中，对各种最终可能导致NK细胞介导的功能活性高或低的参数进行了评估。A/J品系的小鼠表现出非常低的NK细胞肿瘤溶解活性，相应地淋巴瘤发病率很高。相比之下，C57B1/6小鼠表现出相对较高的NK细胞活性，几乎从不发生淋巴瘤。本研究结果显示，A/J小鼠脾脏NK细胞的绝对数量明显低于C57B16/小鼠。此外，A/J小鼠血液中的NK细胞数量比C57B1/6小鼠少得多（30%）。然而，在脾脏富含NK细胞的部分中，具有归巢受体MEL-14或整合素Mac-I的淋巴细胞数量在这两个品系之间没有显著差异，这两种分子都是淋巴细胞从循环系统跨内皮迁移到器官实质所必需的表面分子。此外，两个品系的NK细胞对NK细胞刺激剂全反式维甲酸、吲哚美辛和白细胞介素-2的反应相似。最后，在骨髓（包括NK细胞）中用DNA合成前体3H-胸腺嘧啶进行放射性标记的淋巴细胞数量，这两个品系之间没有显著差异，这表明两个品系骨髓中淋巴细胞的产生水平相当。这些观察结果共同表明，至少在A/J品系小鼠中发现的外周（脾脏、血液）NK细胞介导的功能活性水平低，反映了NK细胞产生后大规模的流产/死亡，或者是抑制NK细胞从骨髓产生部位离开的基于骨髓的微环境缺陷。
