Differentiation and persistence of memory CD8(+) T cells depend on T cell factor 1

Immunity. 2010 Aug 27;33(2):229-40. doi: 10.1016/j.immuni.2010.08.002.


T cell factor 1 (TCF-1) is a transcription factor known to act downstream of the canonical Wnt pathway and is essential for normal T cell development. However, its physiological roles in mature CD8(+) T cell responses are unknown. Here we showed that TCF-1 deficiency limited proliferation of CD8(+) effector T cells and impaired their differentiation toward a central memory phenotype. Moreover, TCF-1-deficient memory CD8(+) T cells were progressively lost over time, exhibiting reduced expression of the antiapoptotic molecule Bcl-2 and interleukin-2 receptor beta chain and diminished IL-15-driven proliferation. TCF-1 was directly associated with the Eomes allele and the Wnt-TCF-1 pathway was necessary and sufficient for optimal Eomes expression in naive and memory CD8(+) T cells. Importantly, forced expression of Eomes partly protected TCF-1-deficient memory CD8(+) T cells from time-dependent attrition. Our studies thus identify TCF-1 as a critical player in a transcriptional program that regulates memory CD8 differentiation and longevity.

Publication types

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

MeSH terms

  • Animals
  • CD8-Positive T-Lymphocytes / cytology*
  • CD8-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / metabolism
  • Cell Differentiation*
  • Gene Expression Regulation
  • Hepatocyte Nuclear Factor 1-alpha
  • Immunologic Memory*
  • Interleukin-15 / immunology
  • Listeria monocytogenes / immunology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Phenotype
  • Protein Binding
  • Regulatory Sequences, Nucleic Acid
  • Signal Transduction
  • T Cell Transcription Factor 1 / deficiency
  • T Cell Transcription Factor 1 / immunology*
  • T Cell Transcription Factor 1 / metabolism
  • T-Box Domain Proteins / genetics
  • T-Box Domain Proteins / metabolism
  • Transcription, Genetic
  • Wnt Proteins / metabolism
  • beta Catenin / metabolism


  • Eomes protein, mouse
  • Hepatocyte Nuclear Factor 1-alpha
  • Hnf1a protein, mouse
  • Interleukin-15
  • T Cell Transcription Factor 1
  • T-Box Domain Proteins
  • Wnt Proteins
  • beta Catenin

Associated data

  • GEO/GSE20754