Redundant functions of TCF-1 and LEF-1 during T and NK cell development, but unique role of TCF-1 for Ly49 NK cell receptor acquisition.
Members of the TCF/LEF (T cell factor / lymphoid enhancer factor) family of DNA-binding factors play important roles during embryogenesis, the establishment and/or maintenance of self-renewing tissues such as the immune system and for malignant transformation. Specifically, it has been shown that TCF-1 is required for T cell development. A role for LEF-1 became apparent when mice harbored two hypomorphic TCF-1 alleles and consequently expressed low levels of TCF-1. Here we show that NK cell development is similarly regulated by redundant functions of TCF-1 and LEF-1, whereby TCF-1 contributes significantly more to NK cell development than LEF-1. Despite this role for NK cell development, LEF-1 is not required for the establishment of a repertoire of MHC class I-specific Ly49 receptors on NK cells. The proper formation of this repertoire depends to a large extent on TCF-1. These findings suggest common and distinct functions of TCF-1 and LEF-1 during lymphocyte development.
Ludwig Institute for Cancer Research, Lausanne Branch and University of Lausanne, Epalinges, Switzerland. wheld@isrec.unil.ch
Werner
W
Held
Hans
H
Clevers
Rudolf
R
Grosschedl
D000818:Animals; D000950:Antigens, Ly / Q000032:analysis*; D004268:DNA-Binding Proteins / Q000502:physiology*; D051538:Hepatocyte Nuclear Factor 1-alpha; D007694:Killer Cells, Natural / Q000502:physiology*; D037181:Lectins, C-Type; D051821:Lymphoid Enhancer-Binding Factor 1; D051379:Mice; D008810:Mice, Inbred C57BL; D055630:Receptors, NK Cell Lectin-Like; D051822:T Cell Transcription Factor 1; D013601:T-Lymphocytes / Q000502:physiology*; D014157:Transcription Factors / Q000502:physiology*
D000950:Antigens, Ly; D004268:DNA-Binding Proteins; D051538:Hepatocyte Nuclear Factor 1-alpha; C496488:Hnf1a protein, mouse; D037181:Lectins, C-Type; C497574:Lef1 protein, mouse; D051821:Lymphoid Enhancer-Binding Factor 1; D055630:Receptors, NK Cell Lectin-Like; D051822:T Cell Transcription Factor 1; D014157:Transcription Factors