Human naive CD8 T cells down-regulate expression of the WNT pathway transcription factors lymphoid enhancer binding factor 1 and transcription factor 7 (T cell factor-1) following antigen encounter in vitro and in vivo

Tim Willinger, Tom Freeman, Mark Herbert, Hitoshi Hasegawa, Andrew J McMichael, Margaret F C Callan

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

The transcription factors lymphoid enhancer binding factor 1 (LEF1) and transcription factor 7 (TCF7) (T cell factor-1 (TCF-1)) are downstream effectors of the WNT signaling pathway, which is a critical regulator of T cell development in the thymus. In this study, we show that LEF1 and TCF7 (TCF-1) are not only expressed in thymocytes, but also in mature T cells. Our data demonstrate that Ag encounter in vivo and engagement of the TCR or IL-15 receptor in vitro leads to the down-regulation of LEF1 and TCF7 (TCF-1) expression in human naive CD8 T cells. We further show that resting T cells preferentially express inhibitory LEF1 and TCF7 (TCF-1) isoforms and that T cell activation changes the isoform balance in favor of stimulatory TCF7 (TCF-1) isoforms. Altogether, our study suggests that proteins involved in the WNT signaling pathway not only regulate T cell development, but also peripheral T cell differentiation.
Original languageEnglish
Pages (from-to)1439-46
Number of pages8
JournalThe Journal of Immunology
Volume176
Issue number3
Publication statusPublished - 1 Feb 2006

Keywords / Materials (for Non-textual outputs)

  • Antigens
  • CD8-Positive T-Lymphocytes
  • Cell Differentiation
  • Cells, Cultured
  • Down-Regulation
  • G0 Phase
  • Gene Expression Profiling
  • Humans
  • Interleukin-15
  • Lymphoid Enhancer-Binding Factor 1
  • Protein Isoforms
  • Receptors, Antigen, T-Cell
  • Signal Transduction
  • T Cell Transcription Factor 1
  • T-Lymphocyte Subsets
  • Wnt Proteins

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