Abstracts (complete list) - Wissenschaft Online

Annette I. Garbe, Taras Kreslavsky, Harald von Boehmer
Role of Notch in survival, proliferation and differentiation of
alpha beta T cell precursors
Notch signaling can synergize with both the pre-TCR and the gamma delta TCR to
determine alpha beta lineage commitment. In case of gamma delta TCR expressing
precursors the selected cells terminate gamma delta TCR expression and undergo Tcra
rearrangement. Under physiological conditions gamma delta TCR expressing precursors
have a competitive disadvantage to pre-TCR expressing cells. In recent studies we could
show that precursors with a gamma delta TCR compete poorly for Notch ligands
because they compete better with pre-TCR expressing cells when offered an excess of
soluble ligands. Overexpression of intracellular Notch abolishes the competitive
advantage entirely. Our results indicate that Notch signaling is not only essential for
survival of DN3 precursors of alpha beta lineage cells but is essentially required for
proliferation of DN3 and DN4 cells. The synergy of TCR and Notch signals becomes
visible in increased CD5 expression that can be diminished by specifically interfering
with Notch signaling. Preliminary data indicate that Notch signaling does not only
contribute to alpha beta lineage choice by helping survival and proliferation of precursor
cells: The differentiation into CD4+CD8+ alpha beta lineage cells of DN3 precursors
with increased survival because of Bcl-2 overexpression still requires Notch signaling
indicating that Notch contributes to survival, proliferation as well as differentiation of
alpha beta lineage precursors.