Selective natural killer resistance in a clone of YAC lymphoma cells.
Selective natural killer resistance in a clone of YAC lymphoma cells.
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YAC 淋巴瘤细胞克隆中的选择性自然杀伤细胞耐药性。
DOI：
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发表时间：
1981
影响因子：
11.1
通讯作者：
D. Kozbor
中科院分区：
文献类型：
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作者：
J. Roder;T. Beaumont;R. Kerbel;T. Haliotis;D. Kozbor
用诱变剂n -甲基-n′-硝基-n -亚硝基胍处理YAC淋巴瘤细胞，克隆和亚克隆。51个无性系中，选择3个进行进一步研究。裂解YAC克隆6和亚克隆6-28细胞需要的NK效应细胞数量是克隆19细胞或YAC亲本细胞系的10倍。即使在长时间孵育（20小时）后，nk抗性（NKR）变异（20%）的细胞溶解最高平台水平也从未接近nk敏感（NKS）变异或YAC亲本细胞（60%）。在未使用诱变剂的克隆YAC细胞上，NKR变异出现的频率相同（0.10），但这些变异在NK敏感性方面高度不稳定，没有进一步研究。NKR和NKS系的细胞溶解均由尼龙-非贴壁asialo-GM1+效应细胞和poly(I)效应细胞介导。poly(C)增强小鼠优先裂解NKS细胞系。NKR的改变似乎没有改变NK靶结构（NK- ts）：(i)未标记的NKR细胞与NKS细胞在互惠的未标记靶竞争分析中平等竞争；（ii）靶效应器偶联物的频率与NKR或NKS系相同；（iii）正常兔血清，含有被认为与NK-TS反应的抗体，对NKR和NKS靶标的反应相同。NKR的改变对NK细胞是选择性的，一般不会导致对裂解的抗性；NKR和NKS变体同样容易受到(i)同种免疫或凝集素依赖效应T细胞介导的细胞溶解和（ii）抗体和补体介导的细胞溶解。这些结果与NKR变异在靶细胞膜上有一个改变的受体位点的假设是一致的，该受体位点通常与效应细胞传递的“溶解片段”结合。
YAC lymphoma cells were treated with the mutagen N-methyl-N'-nitro-N-nitrosoguanidine and then cloned and subcloned. Of 51 clones, 3 were selected for further study. Ten-fold more natural killer (NK) effector cells were required to lyse YAC clone 6 and subclone 6-28 cells compared with clone 19 cells or the YAC parent cell line. The maximum plateau level of cytolysis of the NK-resistant (NKR) variants (20%) never approached that of the NK-sensitive (NKS) variants or YAC parental cells (60%) even after prolonged incubation (20 hr). NKR variants appeared with equal frequency (0.10) on cloning YAC cells that had not been treated with mutagen but these variants were highly unstable with respect to NK sensitivity and were not studied further. Cytolysis of both NKR and NKS lines was mediated by nylon-nonadherent asialo-GM1+ effector cells, and effectors from poly(I) . poly(C)-boosted mice preferentially lysed the NKS lines. The NKR alteration did not appear to change the NK target structure (NK-TS): (i) unlabeled NKR cells competed equally with NKS cells in reciprocal unlabeled-target competition assays; (ii) the frequency of target--effector conjugates was identical with NKR or NKS lines; and (iii) normal rabbit serum, which contains antibodies thought to react with the NK-TS, reacted equally against both NKR and NKS targets. The NKR alteration was selective for NK cells and did not result in a resistance to lysis in general; NKR and NKS variants were equally susceptible to (i) cytolysis mediated by alloimmune or lectin-dependent effector T cells and (ii) antibody- and complement-mediated lysis. These results are compatible with the hypothesis that the NKR variants have an altered acceptor site on the target cell membrane that normally binds the "lytic moiety" delivered by the effector cell.