Abstract
Regulatory T cells engage in the maintenance of immunological self-tolerance by actively suppressing self-reactive lymphocytes. Little is known, however, about the molecular mechanism of their development. Here we show that Foxp3, which encodes a transcription factor that is genetically defective in an autoimmune and inflammatory syndrome in humans and mice, is specifically expressed in naturally arising CD4+ regulatory T cells. Furthermore, retroviral gene transfer of Foxp3 converts naïve T cells toward a regulatory T cell phenotype similar to that of naturally occurring CD4+ regulatory T cells. Thus, Foxp3 is a key regulatory gene for the development of regulatory T cells.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Antigens, CD / analysis
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Autoimmune Diseases / immunology
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Autoimmune Diseases / prevention & control
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CD4-Positive T-Lymphocytes / immunology
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Cytokines / biosynthesis
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DNA-Binding Proteins / genetics
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DNA-Binding Proteins / metabolism*
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Forkhead Transcription Factors
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Gastritis / immunology
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Gastritis / prevention & control
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Immune Tolerance*
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Inflammatory Bowel Diseases / immunology
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Inflammatory Bowel Diseases / prevention & control
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Lymphocyte Activation
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Mice
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Mice, Inbred BALB C
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Mice, SCID
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Mice, Transgenic
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Mutation
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Receptors, Antigen, T-Cell / immunology
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Receptors, Interleukin-2 / analysis
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Recombinant Fusion Proteins / metabolism
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Self Tolerance
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T-Lymphocyte Subsets / cytology
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T-Lymphocyte Subsets / immunology
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T-Lymphocytes / immunology
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T-Lymphocytes, Regulatory / immunology*
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T-Lymphocytes, Regulatory / metabolism*
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Thymus Gland / cytology
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Thymus Gland / metabolism
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Transduction, Genetic
Substances
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Antigens, CD
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Cytokines
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DNA-Binding Proteins
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Forkhead Transcription Factors
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Foxp3 protein, mouse
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Receptors, Antigen, T-Cell
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Receptors, Interleukin-2
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Recombinant Fusion Proteins