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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Lymphoid development in mice with a targeted deletion of the interleukin 2 receptor gamma chain.
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Lymphoid development in mice with a targeted deletion of the interleukin 2 receptor gamma chain.

机译：有针对性地删除白介素2受体γ链的小鼠中的淋巴发育。

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The interleukin 2 receptor gamma chain (IL-2R gamma) is a component of the receptors for IL-2, IL-4, IL-7, and IL-15. Mutations in IL-2R gamma in man appear responsible for the X chromosome-linked immunodeficiency SCIDX1, characterized by a defect in T-cell and natural killer (NK)-cell differentiation with the presence of poorly functioning B cells. To explore at which level IL-2R gamma affects lymphoid development in vivo, we have analyzed mice derived from embryonic stem (ES) cells with mutant IL-2R gamma loci generated by Cre/loxP-mediated recombination. In the peripheral blood of chimeric animals, lymphoid cells derived from IL-2R gamma- ES cells were not detected, although control ES cells carrying an IL-2R gamma gene with embedded loxP sites gave rise to T-, B-, and NK-cell lineages. Germline IL-2R gamma-deficient male animals, however, developed some mature splenic B and T cells, although the absolute number of lymphocytes was almost 10-fold reduced. In contrast, there was a complete disappearance of NK cells (over 350-fold reduction). Development of gut-associated intraepithelial lymphocytes was also severely diminished, and Peyer's patches were not detected. In vitro mitogenic responses of thymocytes, IL-4-directed immunoglobulin class switch of splenocytes, and NK activity were defective. Thus, IL-2R gamma facilitates mainstream B- and T-cell generation and function and also appears to be essential for NK-cell development.
机译：白介素2受体γ链（IL-2Rγ）是IL-2，IL-4，IL-7和IL-15的受体的组成部分。人中IL-2Rγ的突变似乎是造成X染色体连锁的免疫缺陷SCIDX1的特征，其特征是T细胞和自然杀伤（NK）细胞分化存在缺陷，而B细胞功能欠佳。为了探索IL-2Rγ在体内影响淋巴样发育的水平，我们分析了源自胚胎干（ES）细胞的小鼠，该小鼠具有通过Cre / loxP介导的重组产生的突变IL-2Rγ基因座。在嵌合动物的外周血中，尽管携带带有带有loxP位点的IL-2Rγ基因的对照ES细胞产生了T-，B-和NK-，但未检测到源自IL-2Rγ-ES细胞的淋巴样细胞。细胞谱系。然而，生殖细胞IL-2R缺乏γ的雄性动物发育出一些成熟的脾脏B和T细胞，尽管淋巴细胞的绝对数量减少了近10倍。相反，NK细胞完全消失（减少了350倍以上）。肠道相关的上皮内淋巴细胞的发育也被严重减少，并且未检测到派伊尔氏斑。胸腺细胞的体外促有丝分裂反应，脾细胞的IL-4定向免疫球蛋白类别转换和NK活性均存在缺陷。因此，IL-2Rγ促进了主流的B细胞和T细胞的生成和功能，并且似乎对NK细胞的发展至关重要。

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