Negotiation of the T lineage fate decision by transcription-factor interplay and microenvironmental signals

Immunity. 2007 Jun;26(6):690-702. doi: 10.1016/j.immuni.2007.06.005.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Animals
  • B-Lymphocytes / immunology
  • Cell Lineage / immunology*
  • Humans
  • Intracellular Signaling Peptides and Proteins
  • Membrane Proteins / metabolism*
  • Mice
  • Receptors, Notch / metabolism*
  • Signal Transduction
  • Stem Cells / immunology
  • T-Lymphocytes / immunology*
  • Transcription Factors / metabolism*


  • Intracellular Signaling Peptides and Proteins
  • Membrane Proteins
  • Receptors, Notch
  • Transcription Factors
  • delta protein