Abstract
Naive CD4 T cells can develop into regulatory T cells by acquiring the transcription factor Foxp3. Combined signals from the TCR, CD28, IL-2R, and TGF-beta R promote Foxp3 expression in activated naive CD25(-) CD4 T cells. Here we show that OX40 (CD134) signaling inhibits TGF-beta-driven Foxp3 mRNA and suppresses the conversion of naive Ag-specific transgenic CD4 T cells into CD25(+)Foxp3(+) T cells. These data identify OX40 as a negative regulator of Foxp3 and suggest that OX40 can concomitantly promote effector T cell generation while antagonizing the differentiation of adaptive Foxp3(+) regulatory T cells.
Publication types
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Research Support, N.I.H., Extramural
MeSH terms
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Animals
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Antigens / physiology*
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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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Cell Differentiation / immunology
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Cells, Cultured
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Forkhead Transcription Factors / antagonists & inhibitors
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Forkhead Transcription Factors / biosynthesis
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Growth Inhibitors / physiology*
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Humans
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Interleukin-2 Receptor alpha Subunit / antagonists & inhibitors
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Interleukin-2 Receptor alpha Subunit / biosynthesis
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Mice
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Mice, Inbred C57BL
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Mice, Transgenic
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Receptors, OX40 / physiology*
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Resting Phase, Cell Cycle / immunology
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Signal Transduction / 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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Transforming Growth Factor beta / antagonists & inhibitors*
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Transforming Growth Factor beta / physiology
Substances
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Antigens
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Forkhead Transcription Factors
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Foxp3 protein, mouse
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Growth Inhibitors
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Interleukin-2 Receptor alpha Subunit
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Receptors, OX40
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Tnfrsf4 protein, mouse
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Transforming Growth Factor beta