Differential synergy of Notch and T cell receptor signaling determines αβ versus γδ lineage fate
Differential synergy of Notch and T cell receptor signaling determines αβ versus γδ lineage fate
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DOI：
10.1084/jem.20060474
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发表时间：
2006-06-12
影响因子：
15.3
通讯作者：
von Boehmer, Harald
中科院分区：
文献类型：
--
作者：
Garbe, Annette I.;Krueger, Andreas;von Boehmer, Harald
表达前T细胞受体(TCR)、γδTCR或αβTCR的胸腺前体都可以进入CD(4+)8(+)αβ谱系，尽管功效不同。这里显示，具有不同 TCR 的前体细胞增殖和分化为 αβ 谱系细胞需要胸腺发育 DN3 阶段的 Notch 信号传导。在 DN4 阶段，Notch 信号传导仍然对 alpha beta T 细胞的生成有显着贡献。特别是，在αβ谱系定型中，前TCR比其他两种TCR更有效地与Notch信号协同作用，而表达γδTCR的细胞可以在没有Notch信号的情况下存活和扩增，即使Notch信号增强它们的增殖。这些观察结果提出了αβ与γδ谱系选择的新模型，其中谱系命运由TCR和Notch信号传导之间的协同程度决定，并且在进化上最近出现的细胞自主信号传导前TCR增加了αβT细胞生成的功效。
Thymic precursors expressing the pre-T cell receptor ( TCR), the gamma delta TCR, or the alpha beta TCR can all enter the CD(4+)8(+) alpha beta lineage, albeit with different efficacy. Here it is shown that proliferation and differentiation of precursors with the different TCRs into alpha beta lineage cells require Notch signaling at the DN3 stage of thymic development. At the DN4 stage, Notch signaling still significantly contributes to the generation of alpha beta T cells. In particular, in alpha beta lineage commitment, the pre-TCR synergizes more efficiently with Notch signals than the other two TCRs, whereas gamma delta TCR-expressing cells can survive and expand in the absence of Notch signals, even though Notch signaling enhances their proliferation. These observations suggest a new model of alpha beta versus gamma delta lineage choice in which lineage fate is determined by the extent of synergy between TCR and Notch signaling and in which the evolutionarily recent advent of the cell-autonomously signaling pre-TCR increased the efficacy of alpha beta T cell generation.