Identification of novel lymphoid tissues in murine intestinal mucosa where clusters of c-kit+ IL-7R+ Thy1+ lympho-hemopoietic progenitors develop.
Identification of novel lymphoid tissues in murine intestinal mucosa where clusters of c-kit+ IL-7R+ Thy1+ lympho-hemopoietic progenitors develop.
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DOI：
10.1084/jem.184.4.1449
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发表时间：
1996-10-01
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我们已经发现，在小鼠的小肠和大肠粘膜中，可以发现大约1500个微小的簇，其中充满了1000个紧密排列的淋巴细胞。它们位于隐窝固有层（cryptopatches; CP）中，并且可以在出生后14-17天首次检测到。CP中的大部分淋巴细胞表达c-kit、IL-7 R、Thy 1和淋巴细胞功能相关抗原LFA-1，而它们中的大多数保持CD 3-、TCR α β-、TCR γ δ-、sIgM-和B220-。IL-2 R α +、HSA+和Pgp-1+亚群的群体大小可变（20-50%），CD 8+、Ly-1+和CD 4+亚群的组成较小，但也可变（3-20%）。在小肠中，CP不含经历凋亡的细胞，也不含携带RAG-1分子的细胞，但含有携带CD 11 c/CD 18分子的树突状基质细胞。CP中DNA复制细胞的频率高于Peyer集合淋巴结（PP），低于胸腺皮质，与胸腺髓质几乎相当。老年小鼠（> 114周）的CP数量保持不变，但在雌激素治疗后增加一倍，尽管在两种情况下胸腺都急剧减弱。因此，就组织发生、淋巴细胞组成和组织水平的细胞行为而言，PP、孤立淋巴滤泡、外周淋巴结和胸腺均与CP不同。最后，CP在IL-7 R缺陷小鼠的固有层中几乎不存在，这些小鼠的胸腺和外周淋巴细胞结构显著减少。相比之下，CP存在于无菌小鼠和无胸腺（nu/nu）、SCID、TCR β x δ-/-、RAG-2-/-、PP缺陷（aly/aly）、干细胞因子（Sl/Sld）和c-kit（W/Wv）突变小鼠中。综合所有这些结果，CP是第一次鉴定肠道相关小鼠淋巴组织，其中T和/或B细胞后代的IL-7依赖性淋巴造血祖细胞的产生可能在开始断奶的年龄开始发生。
We have revealed that about one and a half thousand tiny clusters, filled with one thousand closely packed lymphocytes, can be found throughout the murine small and large intestinal mucosa. They are located in crypt lamina propria (cryptopatches; CP) and can be first detected at 14-17 d after birth. A large fraction of lymphocytes in CP expresses c-kit, IL-7R, Thy1 and a lymphocyte function-associated antigen, LFA-1, whereas most of them remain CD3-, TCR alpha beta-, TCR gamma delta-, sIgM-, and B220-. The population size of IL-2R alpha+, HSA+ and Pgp-1+ subsets is variable (20-50%) and the composition of CD8+, Ly-1+, and CD4+ subsets is smaller but also variable (3-20%). In the small intestine, CP do not contain cells undergoing apoptosis nor cells bearing RAG-1 molecules, but do contain dendritic stromal cells bearing CD11c/CD18 molecules. The frequency of DNA replicating cells in CP is higher than that in Peyer's patches (PP), is lower than that in the thymic cortex and is almost comparable with that in the thymic medulla. The numbers of CP remain the same in aged mice (> 114 wk) but double after estrogen treatment even though the thymi are attenuated sharply in both conditions. Thus, with respect to histogenesis, lymphocyte composition and tissue level of cellular behavior, neither PP, isolated lymphoid follicles, peripheral LNs, nor thymus are identical with CP. Finally, CP are virtually absent in lamina propria of IL-7R-deficient mice that display a profound reduction in thymic and peripheral lymphoid cellularity. By contrast, CP are present in germ- free mice and in athymic (nu/nu), SCID, TCR beta x delta-/-, RAG-2-/-, PP-deficient (aly/aly), stem cell factor (Sl/Sld) and c-kit (W/Wv) mutant mice. Taking all of these results together, CP are the first identification of gut-associated murine lymphoid tissues where the generation of IL-7-dependent lympho-hematopoietic progenitors for T and/or B cell descendants may start to take place at the age of commencement of weaning.