Abstract
To further understand the interaction among GATA-3, Stat4, and T-bet in helper T cell development, we first showed that retroviral expression of GATA-3 in developing Th1 cells suppresses Th1 development through downregulation of Stat4 rather through downregulation of the IL-12Rbeta2 chain. Correspondingly, Stat4 levels are greatly suppressed during physiological Th2 development. Then, using cells doubly infected with GFP- and YFP-expressing retroviruses, we showed that retroviral GATA-3 expression in developing Th1 cells does not block Th1 development in cells coexpressing Stat4 but does so in cells coexpressing T-bet. Finally, we showed that retroviral Stat4 expression could facilitate Th2-->Th1 conversion in cells bearing an IL-12Rbeta2 transgene, even in cells lacking T-bet. These findings reassert that Stat4 signaling is a central element of Th1/Th2 development.
MeSH terms
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Animals
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Cell Differentiation
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DNA-Binding Proteins / genetics*
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DNA-Binding Proteins / immunology*
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DNA-Binding Proteins / metabolism
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Down-Regulation
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GATA3 Transcription Factor
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Gene Expression
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Interferon-gamma / biosynthesis
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Interleukin-13 / metabolism
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Interleukin-4 / metabolism
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Mice
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Mice, Inbred C57BL
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Mice, Knockout
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Mice, Transgenic
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RNA, Messenger / genetics
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RNA, Messenger / metabolism
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Receptors, Interleukin / genetics
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Receptors, Interleukin-12
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Retroviridae / genetics
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STAT4 Transcription Factor
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T-Box Domain Proteins
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Th1 Cells / cytology
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Th1 Cells / immunology*
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Th1 Cells / metabolism
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Th2 Cells / cytology
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Th2 Cells / immunology
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Th2 Cells / metabolism
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Trans-Activators / genetics*
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Trans-Activators / immunology*
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Trans-Activators / metabolism
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Transcription Factors / genetics
Substances
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DNA-Binding Proteins
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GATA3 Transcription Factor
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Gata3 protein, mouse
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Interleukin-13
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RNA, Messenger
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Receptors, Interleukin
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Receptors, Interleukin-12
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STAT4 Transcription Factor
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Stat4 protein, mouse
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T-Box Domain Proteins
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T-box transcription factor TBX21
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Trans-Activators
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Transcription Factors
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Interleukin-4
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Interferon-gamma