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IL-7 Receptor Signals Inhibit Expression of Transcription Factors TCF-1, LEF-1, and RORt

Qing Yu¹, Batu Erman¹, Jung-Hyun Park¹, Lionel Feigenbaum², and Alfred Singer¹

¹ Experimental Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892
² SAIC-Frederick, National Cancer Institute-Frederick Cancer Research and Development Center, Frederick, MD 21702

Address correspondence to Alfred Singer, Experimental Immunology Branch, National Cancer Institute, National Institutes of Health, Bldg. 10, Rm. 4B36, Bethesda, MD 20892. Phone: (301)-496-5461; Fax: (301)-496-0887; email: SingerA{at}nih.gov

Intrathymic T cell development depends on signals transduced by both T cell receptor and cytokine receptors. Early CD4^–CD8^– (double negative) thymocytes require interleukin (IL)-7 receptor (IL-7R) signals for survival and proliferation, but IL-7R signals are normally extinguished by the immature single positive (ISP) stage of thymocyte development. We now demonstrate that IL-7R signals inhibit expression of transcription factors TCF-1, LEF-1, and RORt that are required for the ISP to double positive (DP) transition in the thymus. In addition, we demonstrate that IL-7R signals also inhibit TCF-1 and LEF-1 expression in mature peripheral T cells. Thus, the present work has identified several important downstream target genes of IL-7R signaling in T cells and thymocytes that provide a molecular mechanism for the inhibitory influence of IL-7R signaling on DP thymocyte development. We conclude that IL-7R signals down-regulate transcription factors required for the ISP to DP transition and so must be terminated by the ISP stage of thymocyte development.

Key Words: ISP thymocytes • IL-7R transgene • developmental arrest

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