From inception to output, Tcf1 and Lef1 safeguard development of T cells and innate immune cells

Immunol Res. 2014 Aug;59(1-3):45-55. doi: 10.1007/s12026-014-8545-9.


Transcription factors have recurring roles during T cell development and activation. Tcf1 and Lef1 are known to be essential for early stages of thymocyte maturation. Recent research has revealed several novel aspects of their functionality. Tcf1 is induced at the very earliest step of specifying hematopoietic progenitors to the T cell lineage as a key target gene downstream of Notch activation. In addition to promoting maturation of T-lineage-committed thymocytes, Tcf1 functions as a tumor suppressor in developing thymocytes, and this is mediated, paradoxically, by restraining Lef1 expression. After positive selection, Tcf1 and Lef1 act together to direct CD4(+)CD8(+) double positive thymocytes to a CD4(+) T cell fate. Although not required for CD8(+) T cell differentiation, Tcf1 and Lef1 cooperate with Runx factors to achieve stable silencing of the Cd4 gene in CD8(+) T cells. Tcf1 is also found to have versatile roles in innate immune cells, which partly mirror its functions in mature T helper cells. Discrepancy in requirements of Tcf1/Lef1 and β-catenin in T cells has been a long-standing enigma. We will review other protein factors interacting with Tcf1 and Lef1 and discuss their regulatory roles independent of β-catenin.

Publication types

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

MeSH terms

  • Animals
  • CD4 Antigens / immunology
  • CD4-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / immunology*
  • Cell Differentiation / immunology*
  • Core Binding Factor alpha Subunits / immunology
  • Hepatocyte Nuclear Factor 1-alpha / immunology*
  • Humans
  • Immunity, Innate / physiology*
  • Lymphoid Enhancer-Binding Factor 1 / immunology*
  • Portraits as Topic
  • Thymocytes / immunology
  • beta Catenin / immunology


  • CD4 Antigens
  • Core Binding Factor alpha Subunits
  • HNF1A protein, human
  • Hepatocyte Nuclear Factor 1-alpha
  • LEF1 protein, human
  • Lymphoid Enhancer-Binding Factor 1
  • beta Catenin