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

Maria Ciofani, Gisèle C. Knowles, David L. Wiest, Harald von Boehmer, Juan Carlos Zúñiga-Pflücker

Research output: Contribution to journalArticlepeer-review

200 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)105-116
Number of pages12
JournalImmunity
Volume25
Issue number1
DOIs
StatePublished - Jul 2006

Keywords

  • CELLIMMUNO

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