Commitment to natural killer cells requires the helix-loop-helix inhibitor Id2
Commitment to natural killer cells requires the helix-loop-helix inhibitor Id2
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DOI：
10.1073/pnas.091537598
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发表时间：
2001-04-24
影响因子：
11.1
通讯作者：
Yokota, Y
中科院分区：
文献类型：
--
作者：
Ikawa, T;Fujimoto, S;Yokota, Y
我们之前已经描述了小鼠胎儿胸腺(FT)中共同的T/NK祖细胞(p-T/NK)是如何产生T和自然杀伤(NK)谱系承诺的，使用能够区分p-T/NK和单一T或NK谱系承诺的祖细胞(分别是p-T和p-NK)的克隆检测系统。然而，控制承诺过程的分子机制尚未确定。在这项研究中，我们研究了表现出NK细胞发育缺陷的Id2(-/-)小鼠的FT细胞的祖细胞活性。在Id2(-/-)FT中，NK细胞大大减少，并且完全缺少野生型胸腺中专含p-NK的细胞群。ID2(-/-)FT祖细胞在IL-2+FT器官培养中不能分化为NK细胞。单个祖细胞分析表明，所有Id2(-/-)胎儿胸腺祖细胞均为T细胞谱系，而在对照组中发现T/NK、T和NK细胞谱系的祖细胞。有趣的是，所分析的Id2(-/-)和Id2(+/+)胚胎的祖细胞总数是相似的。Id2表达与p-NK活性呈正相关。我们的结果表明，Id2在胸腺NK细胞的发育中是不可或缺的，它很可能将双能T/NK祖细胞限制在NK细胞谱系上。
We have previously described how T and natural killer(NK) lineage commitment proceeds from common T/NK progenitors (p-T/NK) in the murine fetal thymus (FT), with the use of a clonal assay system capable of discriminating p-T/NK from unipotent T or NK lineage-committed progenitors (p-T and p-NK, respectively). The molecular mechanisms controlling the commitment processes, however, are yet to be defined. In this study, we investigated the progenitor activity of FT cells from Id2(-/-) mice that exhibit defective NK cell development. In the Id2(-/-) FT, NK cells were greatly reduced, and a cell population that exclusively contains p-NK in the wild-type thymus was completely missing. Id2(-/-) FT progenitors were unable to differentiate into NK cells in IL-2-supplemented-FT organ culture. Single progenitor analysis demonstrated that all Id2(-/-) fetal thymic progenitors are destined for the T cell lineage, whereas progenitors for T/NK, T, and NK cell lineages were found in the control. Interestingly, the total progenitor number was similar between Id2(-/-) and Id2(+/+) embryos analyzed. Expression of Id2 was correlated with p-NK activity. Our results suggest that Id2 is indispensable in thymic NK cell development, where it most probably restricts bipotent T/NK progenitors to the NK cell lineage.