Mouse natural killer subsets defined by their target specificity and their ability to be separately rendered unresponsive in vivo.
Mouse natural killer subsets defined by their target specificity and their ability to be separately rendered unresponsive in vivo.
复制标题
小鼠自然杀伤子集由其目标特异性和在体内单独使其无反应的能力定义。
DOI：
10.4049/jimmunol.158.6.2616
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发表时间：
1997
影响因子：
4.4
通讯作者：
R. Miller
中科院分区：
文献类型：
--
作者：
S. Kung;R. Miller
已知来自F1(AxB)杂交小鼠的NK细胞会排斥来自亲本A或亲本B的骨髓移植(杂交抗性)。在体外杂交抗性试验中使用冷靶竞争，我们在这项工作中证明了亲本A和亲本B被不同的NK亚群杀死。为了证实这些亚群的存在，并确定它们在NK细胞个体发育过程中是否经历了选择/教育过程，我们构建了骨髓嵌合体，其中来自F1小鼠的NK1.1缺失的骨髓细胞被允许在亲本A或亲本B的微环境中成熟。这些重组的嵌合体在YAC-1杀伤和抗体介导的重定向裂解方面显示出正常的NK细胞数量和裂解能力。在体内杂交抗性分析中使用三色流式细胞术分析，我们发现，在A受体(F1-->；A嵌合体)中发展的F1 NK细胞比正常F1或F1-->；F1嵌合体小鼠更有效地清除了A靶，而不是B靶。然而，这些嵌合体细胞的IL-2激活的杀伤细胞培养在体外试验中并没有显示出显著的抗亲本杀伤反应。这些结果表明，NK细胞存在于亚群中，自身反应性NK亚群可被抗辐射宿主元素(S)转为无反应。然而，当NK细胞从体内环境中移除时，这种无反应性可以被打破。
NK cells from F1(AxB) hybrid mice are known to reject bone marrow grafts from either parent A or parent B (hybrid resistance). Using cold target competition in an in vitro hybrid resistance assay, we demonstrate in this work that parent A and parent B are killed by different NK subsets. As confirmation of the existence of these subsets, and to determine whether they undergo a selection/education process during NK cell ontogeny, we constructed bone marrow chimeras in which NK1.1-depleted bone marrow cells from F1 mice were allowed to mature in the microenvironment of either parent A or parent B. These F1-reconstituted chimeras were shown to have normal NK cell numbers and lytic ability in terms of YAC-1 killing and Ab-mediated redirected lysis. Using a three-color flow cytometry analysis in an in vivo hybrid resistance assay, we found that A targets, but not B targets, were less effectively removed by the F1 NK cells that develop in an A recipient (F1-->A chimeras) than in normal F1 or F1-->F1 chimeric mice. IL-2-activated killer cultures of cells from these chimeras, however, did not show a significant difference in the anti-parent killing response in an in vitro assay. These results suggest that NK cells exist in subsets and that self-reactive NK subsets can be rendered unresponsive by radioresistant host element(s). However, this unresponsiveness can be broken when the NK cells are removed from the in vivo environment.