Abstract
Thymus-derived regulatory T cells (Tregs) expressing CD4, CD25, and the transcription factor Foxp3 play major roles in preventing autoimmunity. The Treg population is enriched in T cells expressing high-avidity self-reactive T cell receptors, and thymic epithelial cells expressing self-antigens (Ag) have been implicated in their induction and/or selection. However, the thymic selection events leading to Treg lineage commitment remain unclear. We followed the thymic development of self-Ag-specific Tregs in double-transgenic mice coexpressing a neo-self-Ag, hemagglutinin (HA) under the control of a neural tissue-specific promoter, and a transgenic class II-restricted T cell antigen receptor specific for HA111-119. Our data show that the promiscuous expression of the HA transgene in thymic epithelial cells is involved in the selective induction and/or expansion of HA-specific Foxp3(+) Treg thymic precursors as early as the double-positive stage.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Autoantigens / immunology*
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Cell Differentiation / immunology
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Coculture Techniques
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Forkhead Transcription Factors / metabolism*
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Gene Expression Regulation
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Gene Rearrangement, T-Lymphocyte / immunology
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Glial Fibrillary Acidic Protein / genetics
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Glial Fibrillary Acidic Protein / immunology
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Glial Fibrillary Acidic Protein / metabolism
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Hemagglutinins / genetics
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Hemagglutinins / immunology*
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Hemagglutinins / metabolism
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Immune Tolerance
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Ligands
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Mice
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Mice, Transgenic
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Receptors, Antigen, T-Cell / immunology
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Receptors, Interleukin-2 / immunology*
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T-Lymphocytes, Regulatory / cytology
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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 / immunology*
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Thymus Gland / metabolism
Substances
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Autoantigens
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Forkhead Transcription Factors
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Foxp3 protein, mouse
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Glial Fibrillary Acidic Protein
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Hemagglutinins
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Ligands
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Receptors, Antigen, T-Cell
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Receptors, Interleukin-2