Abstract
Helios, a member of the Ikaros transcription factor family, is preferentially expressed at the mRNA level by regulatory T cells (Treg cells). We evaluated Helios protein expression using a newly generated mAb and demonstrated that it is expressed in all thymocytes at the double negative 2 stage of thymic development. Although Helios was expressed by 100% of CD4(+)CD8(-)Foxp3(+) thymocytes, its expression in peripheral lymphoid tissues was restricted to a subpopulation ( approximately 70%) of Foxp3(+) T cells in mice and humans. Neither mouse nor human naive T cells induced to express Foxp3 in vitro by TCR stimulation in the presence of TGF-beta expressed Helios. Ag-specific Foxp3(+) T cells induced in vivo by Ag feeding also failed to express Helios. Collectively, these results demonstrate that Helios is potentially a specific marker of thymic-derived Treg cells and raises the possibility that a significant percentage of Foxp3(+) Treg cells are generated extrathymically.
Publication types
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Research Support, N.I.H., Intramural
MeSH terms
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Animals
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Cell Differentiation / immunology
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Cell Lineage
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Cell Separation
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DNA-Binding Proteins / biosynthesis
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DNA-Binding Proteins / immunology
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Female
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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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Humans
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Ikaros Transcription Factor / biosynthesis*
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Ikaros Transcription Factor / immunology
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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, Transgenic
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Reverse Transcriptase Polymerase Chain Reaction
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Spleen / cytology
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Spleen / immunology
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T-Lymphocyte Subsets / cytology
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T-Lymphocyte Subsets / immunology
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T-Lymphocyte Subsets / metabolism*
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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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Transcription Factors / biosynthesis
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Transcription Factors / immunology
Substances
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DNA-Binding Proteins
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FOXP3 protein, human
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Forkhead Transcription Factors
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Foxp3 protein, mouse
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IKZF2 protein, human
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Transcription Factors
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Zfpn1a2 protein, mouse
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Ikaros Transcription Factor