T Cell factor 1 represses CD8+ effector T cell formation and function

J Immunol. 2014 Dec 1;193(11):5480-7. doi: 10.4049/jimmunol.1303417. Epub 2014 Oct 29.


The Wnt-responsive transcription factor T cell factor 1 (Tcf1) is well known for its role in thymic T cell development and the formation of memory CD8(+) T cells. However, its role in the initial phases of CD8(+) T effector cell formation has remained unexplored. We report that high levels of Wnt signaling and Tcf1 are operational in naive and memory CD8(+) T cells, whereas Wnt signaling and Tcf1 were low in effector CD8(+) T cells. CD8(+) T cells deficient in Tcf1 produce IFN-γ more rapidly, coinciding with increased demethylation of the IFN-γ enhancer and higher expression of the transcription factors Tbet and Blimp1. Moreover, virus-specific Tcf1(-/-) CD8(+) T cells show accelerated expansion in acute infection, which is associated with increased IFN-γ and TNF production and lower viral load. Genetic complementation experiments with various Tcf1 isoforms indicate that Tcf1 dosage and protein stability are critical in suppressing IFN-γ production. Isoforms lacking the β-catenin binding domain are equally effective in inhibiting CD8(+) effector T cell formation. Thus, Tcf1 functions as a repressor of CD8(+) effector T cell formation in a β-catenin/Wnt-independent manner.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CD8-Positive T-Lymphocytes / immunology*
  • Cells, Cultured
  • Cytotoxicity, Immunologic
  • DNA Methylation
  • Gene Dosage
  • Hepatocyte Nuclear Factor 1-alpha / genetics
  • Hepatocyte Nuclear Factor 1-alpha / metabolism*
  • Immunologic Memory
  • Interferon-gamma / genetics
  • Interferon-gamma / metabolism*
  • Lymphocytic Choriomeningitis / immunology*
  • Lymphocytic choriomeningitis virus / immunology*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Positive Regulatory Domain I-Binding Factor 1
  • Protein Stability
  • Repressor Proteins / genetics
  • Repressor Proteins / metabolism
  • T-Box Domain Proteins / genetics
  • T-Box Domain Proteins / metabolism
  • Up-Regulation
  • Viral Load
  • Virus Diseases


  • HNF1A protein, human
  • Hepatocyte Nuclear Factor 1-alpha
  • Repressor Proteins
  • T-Box Domain Proteins
  • T-box transcription factor TBX21
  • PRDM1 protein, human
  • Interferon-gamma
  • Positive Regulatory Domain I-Binding Factor 1