Negotiation of the T Lineage Fate Decision by Transcription-Factor Interplay and Microenvironmental Signals

Notch-Delta signaling of hematopoietic precursors sets in motion a train of events that activates expression of T lineage genes. Even so, through many cell generations the pro-T cells remain uncommitted to the T cell fate, preserving alternative potentials as divergent as monocyte or dendritic cell fates. This plasticity can be explained by the tenacious expression of stem- and progenitor-associated regulatory genes in the cells, and by the combinatorial coding of T cell identity by factors that are not intrinsically T lineage specific in their spectra of activity. T lineage developmental success depends on precise temporal and quantitative regulation of these factors and on the continuing modulating influence of Notch-Delta signals that buffer the cells against mechanisms promoting non-T outcomes. An additional mechanism, still not fully defined, is required just prior to T cell receptor-mediated selection to end plasticity and make T lineage commitment irreversible