Nature Immunology6, 671 - 679 (2005)
Published online: 12 June 2005; | doi:10.1038/ni1217
There is an Erratum (September 2005) associated with this Article.
Requirement for Notch1 signals at sequential early stages of intrathymic T cell development
Joanne B Tan, Ioana Visan, Julie S Yuan
& Cynthia J Guidos
Program in Developmental Biology, Hospital for Sick Children Research Institute, Toronto, Ontario M5G 1X8, Canada, and Department of Immunology, University of Toronto, Toronto, Ontario M5S 1A8, Canada.
Signaling through the transmembrane Notch1 receptor directs thymus-seeding progenitors (TSPs) to suppress their B cell potential and 'choose' the T cell fate. Present paradigms suggest that TSPs are contained in the multipotent early T lineage precursor (ETP) subset of thymocytes. However, we show here that the B cell potential of ETPs was not augmented in microenvironments that limited Notch1 activation. Furthermore, low-threshold Notch1 signals suppressed B cell production by TSPs before they reached the ETP stage. Notch1 signals of a higher threshold were needed to drive proliferation of ETPs and development into CD4+CD8+ double-positive thymocytes. Thus, TSPs can be differentiated from all previously identified early T cell progenitors by their robust B cell potential and exquisite sensitivity to Notch1 signals.
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