Maintenance of T cell specification and differentiation requires recurrent notch receptor-ligand interactions.
Maintenance of T cell specification and differentiation requires recurrent notch receptor-ligand interactions.
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维持T细胞规范和分化需要经常性的Notch受体 - 配体相互作用。
DOI：
10.1084/jem.20040394
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发表时间：
2004-08-16
影响因子：
15.3
通讯作者：
Zúñiga-Pflücker, JC
中科院分区：
文献类型：
--
作者：
Schmitt, TM;Ciofani, M;Petrie, HT;Zúñiga-Pflücker, JC
Notch信号传导已被证明在诱导T谱系定型中起关键作用。然而，已知T细胞祖细胞在需要Notch信号传导的第一个点之后很长时间内保留其他谱系潜力。因此，Notch信号的额外要求和这些事件相对于胸腺内分化的时间仍然未知。在这里，我们解决这个问题，培养亚群的CD 4-CD 8双阴性（DN）胸腺细胞上控制基质细胞或基质细胞表达δ样1（Dll 1）。发现所有DN亚群都需要Notch信号来分化成CD 4 + CD 8 + T细胞。使用克隆分析，我们表明，CD 44 + CD 25+（DN 2）细胞，这似乎致力于T细胞谱系培养时，Dll 1表达基质细胞，但产生自然杀伤细胞的祖细胞频率类似的CD 44 + CD 25 −（DN 1）胸腺细胞时，Notch信号是不存在的。这些数据，连同Dll 1在整个胸腺皮质的基质细胞上表达的观察结果，表明Notch受体-配体相互作用对于在T细胞发育的DN 1和DN 2阶段诱导和维持T细胞谱系特化是必需的，表明Notch诱导的B细胞命运的抑制与Notch诱导的T谱系定型在时间上是分开的。
Notch signaling has been shown to play a pivotal role in inducing T lineage commitment. However, T cell progenitors are known to retain other lineage potential long after the first point at which Notch signaling is required. Thus, additional requirements for Notch signals and the timing of these events relative to intrathymic differentiation remain unknown. Here, we address this issue by culturing subsets of CD4 CD8 double negative (DN) thymocytes on control stromal cells or stromal cells expressing Delta-like 1 (Dll1). All DN subsets were found to require Notch signals to differentiate into CD4+ CD8+ T cells. Using clonal analyses, we show that CD44+ CD25+ (DN2) cells, which appeared committed to the T cell lineage when cultured on Dll1-expressing stromal cells, nonetheless gave rise to natural killer cells with a progenitor frequency similar to that of CD44+ CD25− (DN1) thymocytes when Notch signaling was absent. These data, together with the observation that Dll1 is expressed on stromal cells throughout the thymic cortex, indicates that Notch receptor–ligand interactions are necessary for induction and maintenance of T cell lineage specification at both the DN1 and DN2 stages of T cell development, suggesting that the Notch-induced repression of the B cell fate is temporally separate from Notch-induced commitment to the T lineage.
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DOI：
10.1084/jem.186.2.173
发表时间：
1997-07-21
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Carlyle JR;Michie AM;Furlonger C;Nakano T;Lenardo MJ;Paige CJ;Zúñiga-Pflücker JC
通讯作者：
Zúñiga-Pflücker JC
影响因子：
32.4
作者：
Carlyle, JR;Zúñiga-Pflücker, JC
通讯作者：
Zúñiga-Pflücker, JC
影响因子：
4.4
作者：
Ciofani, M;Schmitt, TM;Zúñiga-Pflücker, JC
通讯作者：
Zúñiga-Pflücker, JC
影响因子：
64.8
作者：
ARDAVIN, C;WU, L;SHORTMAN, K
通讯作者：
SHORTMAN, K
DOI：
10.1073/pnas.95.21.12522
发表时间：
1998-10-13
影响因子：
11.1
作者：
Capone, M;Hockett, RD;Zlotnik, A
通讯作者：
Zlotnik, A