Abstract
CD4 T cells potentiate the inflammatory or humoral immune response through the action of Th1 and Th2 cells, respectively. The molecular basis of the differentiation of these cells from naive T cell precursors is, however, unclear. We found that GATA-3 was selectively expressed in Th2 cells. GATA-3 is expressed at a high level in naive, freshly activated T cells and Th2 lineage cells, but subsides to a minimal level in Th1 lineage cells as naive cells commit to their Th subset. Antisense GATA-3 inhibited the expression of all Th2 cytokine genes in the Th2 clone D10. GATA-3 directly activated an IL-4 promoter-luciferase reporter gene in M12 cells. In transgenic mice, elevated GATA-3 in CD4 T cells caused Th2 cytokine gene expression in developing Th1 cells. Thus, GATA-3 is necessary and sufficient for Th2 cytokine gene expression.
MeSH terms
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Animals
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Base Sequence
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CD4-Positive T-Lymphocytes / immunology*
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Cell Differentiation
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Cell Division
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Cytokines / genetics*
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DNA Primers / genetics
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DNA, Antisense / genetics
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DNA, Antisense / pharmacology
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DNA, Complementary / genetics
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DNA-Binding Proteins / antagonists & inhibitors
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DNA-Binding Proteins / genetics
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DNA-Binding Proteins / metabolism*
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GATA3 Transcription Factor
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Gene Expression
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In Vitro Techniques
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Interleukin-4 / genetics
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Kinetics
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Mice
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Mice, Transgenic
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Phenotype
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Promoter Regions, Genetic
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Receptors, Antigen, T-Cell / metabolism
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Th1 Cells / cytology
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Th1 Cells / immunology
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Th2 Cells / cytology
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Th2 Cells / immunology*
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Trans-Activators / antagonists & inhibitors
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Trans-Activators / genetics
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Trans-Activators / metabolism*
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Transfection
Substances
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Cytokines
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DNA Primers
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DNA, Antisense
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DNA, Complementary
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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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Receptors, Antigen, T-Cell
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Trans-Activators
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Interleukin-4