Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Antibodies, Monoclonal / pharmacology
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Basic Helix-Loop-Helix Transcription Factors
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Calcium-Binding Proteins
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Cell Differentiation / genetics
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Cell Differentiation / immunology
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Cricetinae
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Epithelial Cells / immunology
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Epithelial Cells / metabolism
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Fetus
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Genetic Vectors / immunology
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Genetic Vectors / metabolism
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Helix-Loop-Helix Motifs / immunology
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Homeodomain Proteins / biosynthesis
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Homeodomain Proteins / genetics
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Homeodomain Proteins / physiology*
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Intercellular Signaling Peptides and Proteins
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Lymphocyte Count
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Membrane Proteins / genetics
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Membrane Proteins / immunology
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Membrane Proteins / physiology*
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Mice
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Mice, Inbred C57BL
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Mice, Knockout
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Organ Culture Techniques
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Recombinant Proteins / pharmacology
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Repressor Proteins / genetics
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Repressor Proteins / immunology
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Repressor Proteins / physiology*
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Retroviridae / genetics
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Retroviridae / immunology
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T-Lymphocytes / cytology*
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T-Lymphocytes / immunology*
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T-Lymphocytes / metabolism
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T-Lymphocytes / pathology
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Thymus Gland / cytology*
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Thymus Gland / immunology
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Thymus Gland / metabolism
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Thymus Gland / pathology
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Transcription Factor HES-1
Substances
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Antibodies, Monoclonal
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Basic Helix-Loop-Helix Transcription Factors
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Calcium-Binding Proteins
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Dlk1 protein, mouse
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Hes1 protein, mouse
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Homeodomain Proteins
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Intercellular Signaling Peptides and Proteins
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Membrane Proteins
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Recombinant Proteins
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Repressor Proteins
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Transcription Factor HES-1