Phenotypic plasticity of T cell progenitors upon exposure to Notch ligands.

Phenotypic plasticity of T cell progenitors upon exposure to Notch ligands.
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DOI:
10.1084/jem.20060731
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发表时间:
2006-08-07
期刊:
The Journal of experimental medicine
影响因子:
--
通讯作者:
von Boehmer H
von Boehmer H
中科院分区:
其他
文献类型:
--
作者:
Krueger A;Garbe AI;von Boehmer H

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尽管做出了许多努力,产生 T 细胞的胸腺迁移的性质仍然不清楚,特别是自从人们知道胸腺外谱系阴性、Sca-1 阳性、c-kit 高祖细胞与胸腺内早期 T 细胞祖细胞 (ETP) 的不同之处在于功能潜力和对 Notch 信号传导的依赖。在我们观察到在前 TCRα 调控元件控制下表达人类 CD25 报告基因的胸腺内 T 细胞前体几乎完全具有 ETP 表型后,我们分析了骨髓中表达报告基因的共同淋巴祖细胞 (CLP) 在表达 Delta 样 1 的基质细胞上培养时的表型变化。我们注意到,这些细胞很快就采用了双阴性 (DN)2 胸腺细胞的表型,几乎没有显示 ETP 表型。我们的数据表明,共同淋巴祖细胞(CLP)可能负责骨髓移植后胸腺功能的快速重建,因为血液中的CLP细胞具有快速进入胸腺并成为DN2胸腺细胞的能力。
Despite many efforts, the nature of thymic immigrants that give rise to T cells has remained obscure, especially since it became known that extrathymic lineage-negative, Sca-1–positive, c-kit high progenitor cells differ from intrathymic early T cell progenitors (ETPs) by functional potential and dependence on Notch signaling. After our observation that intrathymic T cell precursors expressing a human CD25 reporter under control of pre-TCRα regulatory elements almost exclusively have the ETP phenotype, we have analyzed the phenotypic changes of reporter-expressing common lymphoid progenitor (CLP) cells in the bone marrow when cultured on Delta-like 1–expressing stromal cells. We note that these quickly adopt the phenotype of double negative (DN)2 thymocytes with little display of the ETP phenotype. Our data suggest that common lymphoid progenitor (CLP) cells could be responsible for the rapid reconstitution of thymus function after bone marrow transplantation since CLP cells in the blood have the capacity to rapidly enter the thymus and become DN2 thymocytes.
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