Abstract
The intrinsic features of naive CD4 T cells that affect their ability to respond to polarizing signals for Th cell differentiation are not well understood. In this study, we show that naive CD4 T cells from mice transgenic for the Hlx gene expressed lower levels of IL-4Ralpha. The down-regulation of IL-4Ralpha diminished IL-4 signaling and the Th2 response and enhanced the Th1 response under suboptimal polarizing conditions. In nontransgenic CD4 T cells, blocking IL-4Ralpha with Abs had the same effect in an Ab dose-dependent manner. Conversely, Hlx haploinsufficiency caused higher expression of IL-4Ralpha to favor Th2 cell differentiation. Thus, the IL-4Ralpha level on naive CD4 T cells is genetically controlled by Hlx and determines the ratio of Th1 and Th2 cell differentiation.
Publication types
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Research Support, N.I.H., Extramural
MeSH terms
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Animals
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Antibodies / pharmacology
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CD4 Lymphocyte Count
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Cell Differentiation / immunology*
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Cells, Cultured
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Cytokines / physiology*
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Dose-Response Relationship, Drug
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Down-Regulation / immunology
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Heterozygote
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Homeodomain Proteins / genetics
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Interleukin-4 / physiology
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Lymphocyte Activation / immunology
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Mice
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Mice, Inbred C57BL
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Mice, Transgenic
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Receptors, Interleukin-4 / antagonists & inhibitors
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Receptors, Interleukin-4 / immunology
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Resting Phase, Cell Cycle / immunology*
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STAT6 Transcription Factor / metabolism
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Signal Transduction / immunology
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Th1 Cells / cytology*
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Th1 Cells / metabolism*
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Th2 Cells / cytology*
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Th2 Cells / metabolism*
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Transcription Factors / genetics
Substances
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Antibodies
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Cytokines
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Hlx protein, mouse
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Homeodomain Proteins
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Receptors, Interleukin-4
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STAT6 Transcription Factor
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Stat6 protein, mouse
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Transcription Factors
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Interleukin-4