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
Copyright policy )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
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.
- Imperial College London United Kingdom
- University of Edinburgh United Kingdom
- University of Oxford United Kingdom
- Chelsea and Westminster Hospital United Kingdom
- John Radcliffe Hospital United Kingdom
Interleukin-15, Lymphoid Enhancer-Binding Factor 1, Gene Expression Profiling, Receptors, Antigen, T-Cell, Down-Regulation, Cell Differentiation, CD8-Positive T-Lymphocytes, Resting Phase, Cell Cycle, G0 Phase, Wnt Proteins, T-Lymphocyte Subsets, T Cell Transcription Factor 1, Humans, Protein Isoforms, Antigens, Cells, Cultured, Signal Transduction
Interleukin-15, Lymphoid Enhancer-Binding Factor 1, Gene Expression Profiling, Receptors, Antigen, T-Cell, Down-Regulation, Cell Differentiation, CD8-Positive T-Lymphocytes, Resting Phase, Cell Cycle, G0 Phase, Wnt Proteins, T-Lymphocyte Subsets, T Cell Transcription Factor 1, Humans, Protein Isoforms, Antigens, Cells, Cultured, Signal Transduction
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