Stage-Specific and Differential Notch Dependency at the αβ and γδ T Lineage Bifurcation

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Signals transduced by Notch receptors are indispensable for T cell specification and differentiation of αβ T lineage cells. However, the role of Notch signals during αβ versus γδ 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 αβ and γδ T cell lineages to the late DN2 to DN3 developmental stages. Accordingly, αβ and γδ 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 (pTαβ or γδ) of the inducing T cell receptor complex, whereas γδ T cells developed from γδTCR-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 αβ and γδ T cells from T cell progenitors. © 2006 Elsevier Inc. All rights reserved.

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Ciofani, M., Knowles, G. C., Wiest, D. L., von Boehmer, H., & Zúñiga-Pflücker, J. C. (2006). Stage-Specific and Differential Notch Dependency at the αβ and γδ T Lineage Bifurcation. Immunity, 25(1), 105–116.

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