Masuda Kyoko, Itoi Manami, Amagai Takashi, Minato Nagahiro, Katsura Yoshimoto, Kawamoto Hiroshi
Department of Immunology and Cell Biology, Graduate School of Biostudies, Kyoto University, Kyoto, Japan.
J Immunol. 2005 Mar 1;174(5):2525-32. doi: 10.4049/jimmunol.174.5.2525.
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.
胸腺定植祖细胞是否定向于T细胞谱系仍存在争议。阻碍胸腺内移植物特征描述的一个主要问题是，迄今为止鉴定出的最早的胸腺内祖细胞不一定代表真正的胸腺内移植物，因为它们的发育潜能应该已经受到与胸腺微环境接触的影响。在本研究中，我们检测了第11天小鼠胎儿发育上最早的胸腺祖细胞的发育潜能。这些细胞位于周围的间充质区域，尚未接触胸腺上皮成分。流式细胞术和免疫组织化学分析表明，这些细胞仅为Lin(-)c-kit(+)IL-7R(+)。有限稀释分析显示，具有T细胞潜能的祖细胞数量丰富，而在第11天胸腺原基区域几乎不存在具有B细胞潜能的祖细胞。克隆分析表明，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前体细胞，这些前体细胞可以克隆容纳高度多样化的TCRβ链。这些结果提供了直接证据，表明局限于T/NK/树突状细胞谱系的祖细胞选择性地迁移到胸腺中。
