Abstract
Expression of peripheral antigens in the thymus has been implicated in T cell tolerance and autoimmunity. Here we identified medullary thymic epithelial cells as being a unique cell type that expresses a diverse range of tissue-specific antigens. We found that this promiscuous gene expression was a cell-autonomous property of medullary epithelial cells and was maintained during the entire period of thymic T cell output. It may facilitate tolerance induction to self-antigens that would otherwise be temporally or spatially secluded from the immune system. However, the array of promiscuously expressed self-antigens appeared random rather than selected and was not confined to secluded self-antigens.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Autoantigens / biosynthesis*
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Autoantigens / genetics
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Autoantigens / immunology
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Bone Marrow Transplantation
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Cells, Cultured / metabolism
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DNA, Complementary / genetics
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DNA-Binding Proteins / deficiency
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DNA-Binding Proteins / genetics
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DNA-Binding Proteins / physiology
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Epithelial Cells / metabolism
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Gene Expression Profiling
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Gene Expression Regulation*
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Male
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Mice
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Mice, Inbred BALB C
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Mice, Inbred C57BL
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Mice, Inbred NOD
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Mice, Transgenic
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Organ Specificity
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Radiation Chimera
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Reverse Transcriptase Polymerase Chain Reaction
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Self Tolerance / genetics*
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Serum Amyloid P-Component / biosynthesis
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Serum Amyloid P-Component / deficiency
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Serum Amyloid P-Component / genetics
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Specific Pathogen-Free Organisms
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Spleen / cytology
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Spleen / metabolism
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Stromal Cells / metabolism
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T-Lymphocyte Subsets / immunology*
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Testis / cytology
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Testis / metabolism
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Thymus Gland / cytology
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Thymus Gland / embryology
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Thymus Gland / metabolism*
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Thymus Gland / transplantation
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Transcription Factors / metabolism
Substances
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Autoantigens
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DNA, Complementary
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DNA-Binding Proteins
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Rag2 protein, mouse
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Serum Amyloid P-Component
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Transcription Factors
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V(D)J recombination activating protein 2