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.
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.
Willinger
Tim
T
Medical Research Council Human Immunology Unit, Weatherall Institute of Molecular Medicine, Oxford, United Kingdom. TimW@hammer.imm.ox.ac.uk
Freeman
Tom
T
Herbert
Mark
M
Hasegawa
Hitoshi
H
McMichael
Andrew J
AJ
Callan
Margaret F C
MF
D000941:Antigens / Q000502:physiology*; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D002478:Cells, Cultured; D015536:Down-Regulation / Q000276:immunology*; D020869:Gene Expression Profiling; D006801:Humans; D019409:Interleukin-15 / Q000502:physiology; D051821:Lymphoid Enhancer-Binding Factor 1 / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000235:genetics; D020033:Protein Isoforms / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics; D011948:Receptors, Antigen, T-Cell / Q000502:physiology; D016192:Resting Phase, Cell Cycle / Q000235:genetics / Q000276:immunology*; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology*; D051822:T Cell Transcription Factor 1 / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000235:genetics; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology; D051153:Wnt Proteins / Q000037:antagonists & inhibitors* / Q000096:biosynthesis
D000941:Antigens; D019409:Interleukin-15; D051821:Lymphoid Enhancer-Binding Factor 1; D020033:Protein Isoforms; D011948:Receptors, Antigen, T-Cell; D051822:T Cell Transcription Factor 1; C497576:TCF7 protein, human; D051153:Wnt Proteins