TY - JOUR
T1 - Stage-Specific and Differential Notch Dependency at the αβ and γδ T Lineage Bifurcation
AU - Ciofani, Maria
AU - Knowles, Gisèle C.
AU - Wiest, David L.
AU - von Boehmer, Harald
AU - Zúñiga-Pflücker, Juan Carlos
PY - 2006/7
Y1 - 2006/7
N2 - 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.
AB - 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.
KW - CELLIMMUNO
UR - http://www.scopus.com/inward/record.url?scp=33745014890&partnerID=8YFLogxK
U2 - 10.1016/j.immuni.2006.05.010
DO - 10.1016/j.immuni.2006.05.010
M3 - Article
C2 - 16814577
SN - 1074-7613
VL - 25
SP - 105
EP - 116
JO - Immunity
JF - Immunity
IS - 1
ER -