Abstract
Autoreactive CD4+ T cells can undergo deletion and/or become CD25+Foxp3+ Treg as they develop intrathymically, but how these alternative developmental fates are specified based on interactions with self-peptide(s) is not understood. We show here that thymocytes expressing an autoreactive TCR can be subjected to varying degrees of deletion that correlate with the amount of self-peptide. Strikingly, among thymocytes that evade deletion, similar proportions acquire Foxp3 expression. These findings provide evidence that Foxp3+ Treg can develop among members of a cohort of autoreactive thymocytes that have evaded deletion by a self-peptide, and that deletion and Treg formation can act together to bias the Treg repertoire toward low-abundance self-peptide(s).
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, Non-P.H.S.
MeSH terms
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Animals
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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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Cells, Cultured
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Clonal Deletion / immunology
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Flow Cytometry
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Forkhead Transcription Factors / immunology
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Forkhead Transcription Factors / metabolism
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Hemagglutinin Glycoproteins, Influenza Virus / genetics
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Hemagglutinin Glycoproteins, Influenza Virus / immunology
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Hemagglutinin Glycoproteins, Influenza Virus / metabolism
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Interleukin-2 Receptor alpha Subunit / immunology
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Interleukin-2 Receptor alpha Subunit / metabolism
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Lymphocyte Activation / immunology
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Mice
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Mice, Inbred BALB C
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Mice, Transgenic
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Peptides / immunology*
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Peptides / metabolism
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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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Reverse Transcriptase Polymerase Chain Reaction
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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*
Substances
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Forkhead Transcription Factors
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Foxp3 protein, mouse
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Hemagglutinin Glycoproteins, Influenza Virus
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Il2ra protein, mouse
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Interleukin-2 Receptor alpha Subunit
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Peptides
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Receptors, Antigen, T-Cell