Stage-specific and differential notch dependency at the alphabeta and gammadelta T lineage bifurcation.
Signals transduced by Notch receptors are indispensable for T cell specification and differentiation of alphabeta T lineage cells. However, the role of Notch signals during alphabeta versus gammadelta 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 alphabeta and gammadelta T cell lineages to the late DN2 to DN3 developmental stages. Accordingly, alphabeta and gammadelta 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 (pTalphabeta or gammadelta) of the inducing T cell receptor complex, whereas gammadelta T cells developed from gammadeltaTCR-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 alphabeta and gammadelta T cells from T cell progenitors.
Duke Scholars
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- Thymus Gland
- T-Lymphocytes
- Signal Transduction
- Receptors, Notch
- Receptors, Antigen, T-Cell
- Mice
- Ligands
- Immunology
- Hepatocytes
- Hematopoietic Stem Cells
Citation
Published In
DOI
ISSN
Publication Date
Volume
Issue
Start / End Page
Location
Related Subject Headings
- Thymus Gland
- T-Lymphocytes
- Signal Transduction
- Receptors, Notch
- Receptors, Antigen, T-Cell
- Mice
- Ligands
- Immunology
- Hepatocytes
- Hematopoietic Stem Cells