Abstract
Immature double-positive thymocytes are generated in the thymic cortex, and on positive selection, are induced to differentiate into mature single-positive thymocytes and relocate to the medulla. CCR7 is pivotal for cortex-to-medulla migration of positively selected thymocytes, and CCR7-mediated migration to the medulla is essential for establishing central tolerance, thereby, preventing tissue-specific autoimmunity. However, it was unclear how CCR7-mediated migration to the medulla affects the establishment of self-tolerance. Here, we show that the deletion of thymocytes specific for insulin-promoter-driven tissue-restricted antigens (TRAs) is significantly impaired in CCR7- or CCR7-ligand-deficient mice. These results indicate that CCR7-mediated migration to the medulla contributes to the negative selection of TRA-reactive thymocytes.
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 / immunology
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Autoimmunity / immunology
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CD4-Positive T-Lymphocytes / cytology
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CD4-Positive T-Lymphocytes / immunology
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CD4-Positive T-Lymphocytes / metabolism
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CD8-Positive T-Lymphocytes / cytology
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CD8-Positive T-Lymphocytes / immunology
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CD8-Positive T-Lymphocytes / metabolism
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Cell Movement / immunology*
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Fluorescent Antibody Technique
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Immune Tolerance / immunology*
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Mice
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Mice, Inbred C57BL
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Mice, Knockout
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Mice, Transgenic
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Receptors, Antigen, T-Cell / genetics
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Receptors, Antigen, T-Cell / immunology
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Receptors, Antigen, T-Cell / metabolism
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Receptors, CCR7 / genetics
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Receptors, CCR7 / immunology*
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Receptors, CCR7 / metabolism
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Signal Transduction / immunology
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Thymus Gland / cytology
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Thymus Gland / immunology*
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Thymus Gland / metabolism
Substances
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Antigens
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Ccr7 protein, mouse
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Receptors, Antigen, T-Cell
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Receptors, CCR7