Journal article

Constitutive Notch signalling promotes CD4(-)CD8(-) thymocyte differentiation in the absence of the pre-TCR complex, by mimicking pre-TCR signals

Alison M Michie, Angela C Chan, Maria Ciofani, Michael Carleton, Juliette M Lefebvre, Yiping He, David M Allman, David L Wiest, Juan Carlos Zuniga-Pfluecker, David J Izon

INTERNATIONAL IMMUNOLOGY | OXFORD UNIV PRESS | Published : 2007

Abstract

Notch1 signalling is essential for the commitment of multipotent lymphocyte precursors towards the alphabeta T-cell lineage and plays an important role in regulating beta-selection in CD4(-)CD8(-) double-negative (DN) thymocytes. However, the role played by Notch in promoting the development of CD4(+)CD8(+) double-positive (DP) thymocytes is poorly characterized. Here, we demonstrate that the introduction of a constitutively active Notch1 (ICN1) construct into RAG(-/-) lymphocyte precursors resulted in the generation of DP thymocytes in in vitro T-cell culture systems. Notably, developmental rescue was dependent not only on the presence of an intact Notch1 RAM domain but also on Delta-like s..

View full abstract

University of Melbourne Researchers