Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Antigens / physiology*
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CD8-Positive T-Lymphocytes / cytology
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CD8-Positive T-Lymphocytes / immunology*
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Cell Differentiation / genetics
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Cell Differentiation / immunology
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Cells, Cultured
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Down-Regulation / immunology*
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Gene Expression Profiling
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Humans
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Interleukin-15 / physiology
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Lymphoid Enhancer-Binding Factor 1 / antagonists & inhibitors*
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Lymphoid Enhancer-Binding Factor 1 / biosynthesis
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Lymphoid Enhancer-Binding Factor 1 / genetics
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Protein Isoforms / antagonists & inhibitors
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Protein Isoforms / biosynthesis
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Protein Isoforms / genetics
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Receptors, Antigen, T-Cell / physiology
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Resting Phase, Cell Cycle / genetics
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Resting Phase, Cell Cycle / immunology*
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Signal Transduction / genetics
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Signal Transduction / immunology*
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T Cell Transcription Factor 1 / antagonists & inhibitors*
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T Cell Transcription Factor 1 / biosynthesis
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T Cell Transcription Factor 1 / genetics
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T-Lymphocyte Subsets / cytology
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T-Lymphocyte Subsets / immunology
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Wnt Proteins / antagonists & inhibitors*
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Wnt Proteins / biosynthesis
Substances
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Antigens
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Interleukin-15
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Lymphoid Enhancer-Binding Factor 1
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Protein Isoforms
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Receptors, Antigen, T-Cell
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T Cell Transcription Factor 1
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TCF7 protein, human
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Wnt Proteins