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Department of Immunology, Institute of Basic Medical Sciences, University of Tsukuba, Tsukuba, Japan;
Kirin Brewery Pharmaceutical Research Laboratory, Gunma, Japan;
Core Research for Evolutional Science and Technology, Japan Science and Technology Corporation, Tsukuba, Japan;
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Department of Biological Structure and Department of Immunology, University of Washington, Seattle, WA 98195;
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Precursory Research of Embryonic Science and Technology (PRESTO), Japan Science and Technology Corporation, Tokushima, Japan; and
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Division of Experimental Immunology, Institute for Genome Research, University of Tokushima, Tokushima, Japan
T lymphocyte development requires a series of interactions between developing thymocytes and thymic epithelial (TE) cells. In this paper we show that TE cells in the developing thymus express Pref-1, a Delta-like cell-surface molecule. In fetal thymus organ cultures (FTOC), thymocyte cellularity was increased by the exogenous dimeric Pref-1 fusion protein, but was reduced by the soluble Pref-1 monomer or anti-Pref-1 Ab. Dimeric Pref-1 in FTOC also increased thymocyte expression of the HES-1 transcription factor. Thymocyte cellularity was increased in FTOC repopulated with immature thymocytes overexpressing HES-1, whereas FTOC from HES-1-deficient mice were hypocellular and unresponsive to the Pref-1 dimer. We detected no effects of either Pref-1 or HES-1 on developmental choice among thymocyte lineages. These results indicate that Pref-1 expressed by TE cells and HES-1 expressed by thymocytes are critically involved in supporting thymocyte cellularity.
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