Stage-specific and differential notch dependency at the αβ and γδ T lineage bifurcation
Stage-specific and differential notch dependency at the αβ and γδ T lineage bifurcation
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DOI：
10.1016/j.immuni.2006.05.010
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发表时间：
2006-07-01
期刊：
影响因子：
32.4
通讯作者：
Zuniga-Pflucker, Juan Carlos
中科院分区：
文献类型：
--
作者：
Ciofani, Maria;Knowles, Gisele C.;Zuniga-Pflucker, Juan Carlos
Notch受体转导的信号对于T细胞的特化和向上T谱系细胞的分化是必不可少的。然而，Notch信号在α β与γ δ T谱系决定中的作用仍然存在争议。在这里，我们通过采用CD 4（-）CD 8（-）（DN）祖细胞潜能的克隆分析来解决这个问题，以将α β和γ δ T细胞谱系的分歧定位于晚期DN 2至DN 3发育阶段。因此，在存在和不存在通过δ样1的Notch信号传导的情况下，确定这些T细胞祖细胞亚群内的α β和γ δ前体频率。发现Notch信号对于DN至CD 4（+）CD 8（+）（DP）的转变是关键的，而不管诱导T细胞受体复合物的身份（pT α β或γ δ）如何，而γ δ T细胞在没有进一步Notch配体相互作用的情况下从表达γ δ TCR的T细胞祖细胞发育。总的来说，我们的研究结果表明，在从T细胞祖细胞分化up和γ δ T细胞时，Notch受体-配体相互作用存在差异性、阶段特异性要求。
Signals transduced by Notch receptors are indispensable for T cell specification and differentiation of up T lineage cells. However, the role of Notch signals during alpha beta versus gamma delta T lineage decision remains controversial. Here, we addressed this question by employing a clonal analysis of CD4(-)CD8(-) (DN) progenitor potential to position the divergence of alpha beta and gamma delta T cell lineages to the late DN2 to DN3 developmental stages. Accordingly, alpha beta and gamma delta precursor frequencies within these T cell progenitor subsets were determined, both in the presence and absence of Notch signaling through Delta-like 1. Notch signals were found to be critical for the DN to CD4(+)CD8(+) (DP) transition, irrespective of the identity (pT alpha beta or gamma delta) of the inducing T cell receptor complex, whereas gamma delta T cells developed from gamma delta TCR-expressing T cell progenitors in the absence of further Notch ligand interaction. Collectively, our findings demonstrate a differential, stage-specific requirement for Notch receptor-ligand interactions in the differentiation of up and gamma delta T cells from T cell progenitors.