Adachi S, Yoshida H, Honda K, Maki K, Saijo K, Ikuta K, Saito T, Nishikawa S I
Molecular Genetics, Faculty of Medicine, Kyoto University, Japan.
Int Immunol. 1998 Jan;10(1):1-6. doi: 10.1093/intimm/10.1.1.
We investigated the role of IL-7 receptor alpha (IL-7Ralpha) signal in the formation of Peyer's patch (PP) anlage. Although pan-lymphopenia is a common phenotype of rag2-/- and il7ralpha-/- mice, a close inspection revealed nodules corresponding to PP in the adult rag2-/- but not in the il7ralpha-/- mouse. In our previous study, three histologically distinct steps in the formation of PP were identified. The first is the appearance of VCAM-1 + spots in the intestine, which probably represents an initial stage of the formation of the PP anlage. Accumulation of cells bearing IL-7Ralpha, CD4 or Ia in this region then follows and eventually entry of mature lymphocytes expressing CD3 or B220 occurs just before birth. Based on this criterion, we next investigated which of these events is defective in mice with severe combined immunodeficiency. Formation of VCAM-1 + spots and cluster formation of IL-7Ralpha+ cells proceed normally in the rag2-/- mouse which completely lacks mature lymphocytes. In contrast, no VCAM-1+ spots were detected in the embryonic nor neonatal il7ralpha-/- mice, suggesting that IL-7Ralpha signal is involved in the early phase of PP anlage formation. The same defect was found in the jak3-/- mouse. In addition to the appearance of VCAM1+ spots, the clustering of IL-7Ralpha+ cells was absent in the jak3-/- mouse, though IL-7Ralpha+ cells are found to scatter over the intestine. These results indicate that IL-7Ralpha is an essential signal for an early step of PP anlage formation, without which the subsequent processes cannot be initiated.
我们研究了白细胞介素-7受体α（IL-7Rα）信号在派尔集合淋巴结（PP）原基形成中的作用。尽管全淋巴细胞减少是rag2-/-和il7ralpha-/-小鼠的常见表型，但仔细观察发现成年rag2-/-小鼠中有对应于PP的结节，而il7ralpha-/-小鼠中则没有。在我们之前的研究中，确定了PP形成过程中的三个组织学上不同的步骤。第一步是肠内出现血管细胞黏附分子-1（VCAM-1）阳性斑点，这可能代表PP原基形成的初始阶段。随后该区域出现携带IL-7Rα、CD4或Ia的细胞聚集，最终在出生前出现表达CD3或B220的成熟淋巴细胞进入。基于这一标准，我们接下来研究了严重联合免疫缺陷小鼠中这些事件中的哪一个存在缺陷。在完全缺乏成熟淋巴细胞的rag2-/-小鼠中，VCAM-1阳性斑点的形成和IL-7Rα阳性细胞的聚集正常进行。相比之下，在胚胎期和新生期的il7ralpha-/-小鼠中均未检测到VCAM-1阳性斑点，这表明IL-7Rα信号参与了PP原基形成的早期阶段。在jak3-/-小鼠中也发现了同样的缺陷。除了出现VCAM1阳性斑点外，jak3-/-小鼠中没有IL-7Rα阳性细胞的聚集，尽管发现IL-7Rα阳性细胞散布在肠道中。这些结果表明，IL-7Rα是PP原基形成早期阶段的必需信号，没有它，后续过程就无法启动。
