TCF-1 and LEF-1 act upstream of Th-POK to promote the CD4(+) T cell fate and interact with Runx3 to silence Cd4 in CD8(+) T cells

Nat Immunol. 2014 Jul;15(7):646-656. doi: 10.1038/ni.2897. Epub 2014 May 18.


The transcription factors TCF-1 and LEF-1 are essential for early T cell development, but their roles beyond the CD4(+)CD8(+) double-positive (DP) stage are unknown. By specific ablation of these factors in DP thymocytes, we demonstrated that deficiency in TCF-1 and LEF-1 diminished the output of CD4(+) T cells and redirected CD4(+) T cells to a CD8(+) T cell fate. The role of TCF-1 and LEF-1 in the CD4-versus-CD8 lineage 'choice' was mediated in part by direct positive regulation of the transcription factor Th-POK. Furthermore, loss of TCF-1 and LEF-1 unexpectedly caused derepression of CD4 expression in T cells committed to the CD8(+) lineage without affecting the expression of Runx transcription factors. Instead, TCF-1 physically interacted with Runx3 to cooperatively silence Cd4. Thus, TCF-1 and LEF-1 adopted distinct genetic 'wiring' to promote the CD4(+) T cell fate and establish CD8(+) T cell identity.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CD4 Antigens / physiology*
  • CD4-Positive T-Lymphocytes / physiology*
  • CD8-Positive T-Lymphocytes / physiology*
  • Cell Lineage
  • Core Binding Factor Alpha 3 Subunit / physiology*
  • Female
  • Hepatocyte Nuclear Factor 1-alpha
  • Lymphoid Enhancer-Binding Factor 1 / physiology*
  • Male
  • Mice
  • T Cell Transcription Factor 1 / physiology*
  • Transcription Factors / physiology*


  • CD4 Antigens
  • Core Binding Factor Alpha 3 Subunit
  • Hepatocyte Nuclear Factor 1-alpha
  • Hnf1a protein, mouse
  • Lef1 protein, mouse
  • Lymphoid Enhancer-Binding Factor 1
  • Runx3 protein, mouse
  • T Cell Transcription Factor 1
  • Th-POK protein, mouse
  • Transcription Factors

Associated data

  • GEO/GSE52070
  • GEO/GSM1258235
  • GEO/GSM1258236