Abstract
Thymocyte development is a tightly regulated process. CD4+CD8+ double-positive (DP) immature thymocytes exhibit distinct phenotypic features from mature T cells; they express only 10% of surface TCR that are found on mature T cells and do not proliferate and produce IL-2 in response to stimulation. In this report we show that transgenic expression of the orphan nuclear receptor ROR gamma t in mature T cells down-regulates their surface TCR expression. The ROR gamma t transgene inhibits IL-2 production by mature T cells, and this inhibition may be partially due to the inhibitory effect of ROR gamma t on c-Rel transcription. Furthermore, ectopic expression of ROR gamma t inhibits the proliferation of mature and immature T cells. These results, together with its predominant expression in DP thymocytes, suggest that ROR gamma t controls these distinct phenotypic features of DP thymocytes. Our data suggest that down-regulation of ROR gamma t expression in thymocytes is essential for their maturation.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Cell Differentiation / genetics
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Cell Differentiation / immunology
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Crosses, Genetic
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Down-Regulation / genetics
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Down-Regulation / immunology*
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Fas Ligand Protein
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Gene Expression Regulation / immunology
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Immunosuppressive Agents / pharmacology
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Interleukin-2 / antagonists & inhibitors
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Interleukin-2 / biosynthesis
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Ligands
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Lymphocyte Activation / immunology
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Membrane Glycoproteins / biosynthesis
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Mice
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Mice, Inbred C57BL
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Mice, Inbred CBA
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Mice, Transgenic
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Nuclear Receptor Subfamily 1, Group F, Member 3
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Proto-Oncogene Proteins c-rel / antagonists & inhibitors
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Proto-Oncogene Proteins c-rel / biosynthesis
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Receptors, Antigen, T-Cell / antagonists & inhibitors
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Receptors, Antigen, T-Cell / biosynthesis
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Receptors, Cytoplasmic and Nuclear / biosynthesis*
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Receptors, Cytoplasmic and Nuclear / genetics
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Receptors, Cytoplasmic and Nuclear / physiology
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Receptors, Retinoic Acid*
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Receptors, Thyroid Hormone*
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T-Lymphocyte Subsets / cytology*
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T-Lymphocyte Subsets / immunology
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T-Lymphocyte Subsets / metabolism*
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Thymus Gland / cytology
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Thymus Gland / metabolism
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Transgenes / immunology
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Up-Regulation / genetics
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Up-Regulation / immunology
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fas Receptor / metabolism
Substances
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Fas Ligand Protein
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Fasl protein, mouse
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Immunosuppressive Agents
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Interleukin-2
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Ligands
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Membrane Glycoproteins
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Nuclear Receptor Subfamily 1, Group F, Member 3
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Proto-Oncogene Proteins c-rel
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Receptors, Antigen, T-Cell
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Receptors, Cytoplasmic and Nuclear
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Receptors, Retinoic Acid
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Receptors, Thyroid Hormone
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Rorc protein, mouse
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fas Receptor