Thymic anlage is colonized by progenitors restricted to T, NK, and dendritic cell lineages
Thymic anlage is colonized by progenitors restricted to T, NK, and dendritic cell lineages
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DOI：
10.4049/jimmunol.174.5.2525
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发表时间：
2005-03-01
影响因子：
4.4
通讯作者：
Kawamoto, H
中科院分区：
文献类型：
--
作者：
Masuda, K;Itoi, M;Kawamoto, H
胸腺定植祖细胞是否属于T细胞谱系仍然存在争议。阻碍胸腺移民特征的一个主要问题是，迄今为止发现的最早的胸腺内祖先并不一定代表真正的胸腺移民，因为他们的发育潜力应该受到与胸腺微环境接触的影响。在本研究中，我们研究了第11天小鼠胎儿的最早胸腺祖细胞的发育潜力。这些细胞位于周围的间充质区，没有遇到胸腺上皮成分。流式细胞术和免疫组织化学分析表明，这些细胞完全是Lin(-)c-kit(+)IL-7R（+）。限制性稀释分析显示，具有T细胞潜能的祖细胞丰富，而具有B细胞潜能的祖细胞在第11天胸腺样本区几乎不存在。克隆分析显示它们仅限于T、NK和树突状细胞谱系。每个祖细胞都能够形成大量的前体，这些前体可以克隆地容纳高度多样化的tcrβ链。这些结果提供了直接证据，证明限制于T/NK/树突状细胞谱系的祖细胞选择性地迁移到胸腺。
It remains controversial whether the thymus-colonizing progenitors are committed to the T cell lineage. A major problem that has impeded the characterization of thymic immigrants has been that the earliest intrathymic progenitors thus far identified do not necessarily represent the genuine thymic immigrants, because their developmental potential should have been influenced by contact with the thymic microenvironment. In the present study, we examined the developmental potential of the ontogenically earliest thymic progenitors of day 11 murine fetus. These cells reside in the surrounding mesenchymal region and have not encountered thymic epithelial components. Flow cytometric and immunohistochemical analyses demonstrated that these cells are exclusively Lin(-)c-kit(+)IL-7R(+). Limiting dilution analyses disclosed that the progenitors with T cell potential were abundant, while those with B cell potential were virtually absent in the region of day 11 thymic anlage. Clonal analyses reveled that they are restricted to T, NK, and dendritic cell lineages. Each progenitor was capable of forming a large number of precursors that may clonally accommodate highly diverse TCRbeta chains. These results provide direct evidence that the progenitors restricted to the T/NK/dendritic cell lineage selectively immigrate into the thymus.