Obligatory role for cooperative signaling by pre-TCR and notch during thymocyte differentiation
Obligatory role for cooperative signaling by pre-TCR and notch during thymocyte differentiation
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DOI：
10.4049/jimmunol.172.9.5230
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发表时间：
2004-05-01
影响因子：
4.4
通讯作者：
Zúñiga-Pflücker, JC
中科院分区：
文献类型：
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作者：
Ciofani, M;Schmitt, TM;Zúñiga-Pflücker, JC
T细胞发育过程中的第一个检查点，被称为β选择，需要tcr - β基因位点的成功重排。Notch信号在T淋巴形成的各个阶段都有涉及。然而，尚不清楚Notch受体-配体相互作用在β选择过程中是否必要。本研究表明，小鼠CD4(-)CD8（-）胸腺细胞向CD4(+)CD8（+）阶段的生存、增殖和分化需要tcr前信号与Notch受体和Delta-like-1配体的相互作用。此外，我们解决了β选择的最小信号要求，并显示了关键近端信号分子的分层定位。总的来说，我们的研究结果表明Notch受体-配体相互作用在实现tcr前复合物的自主信号传导能力方面发挥了重要作用。
The first checkpoint during T cell development, known as beta selection, requires the successful rearrangement of the TCR-beta gene locus. Notch signaling has been implicated in various stages during T lymphopoiesis. However, it is unclear whether Notch receptor-ligand interactions are necessary during beta selection. Here, we show that pre-TCR signaling concurrent with Notch receptor and Delta-like-1 ligand interactions are required for the survival, proliferation, and differentiation of mouse CD4(-)CD8(-) thymocytes to the CD4(+)CD8(+) stage. Furthermore, we address the minimal signaling requirements underlying beta selection and show a hierarchical positioning of key proximal signaling molecules. Collectively, our results demonstrate an essential role for Notch receptor-ligand interactions in enabling the autonomous signaling capacity of the pre-TCR complex.