Abstract
Cluster of differentation (CD)4+ T helper cells (Th)1s fail to produce interleukin (IL)-4. Even if restimulated in the presence of IL-4, a condition that induces IL-4-producing capacity in naive CD4+ T cells, Th1s fail to become IL-4 producers. We report that Th1 cells have a major impairment in IL-4 signaling. When compared to both Th2s and naive T cells, they display a striking diminution in phosphorylation of Stat6. They also show reduced phosphorylation of Janus kinase (JAK)-3 and insulin receptor substrate (IRS)-2 when compared to Th2s. Stat6 and JAK-3 are present in equivalent amounts in Th1s and Th2s, but IRS-2 protein levels are much lower in Th1s than in Th2s. Altered sensitivity to IL-4, the major inducer of the Th2 phenotype, may explain the stability of the Th1 state.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Cells, Cultured
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Dose-Response Relationship, Drug
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Insulin Receptor Substrate Proteins
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Interleukin-4 / metabolism*
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Interleukin-4 / pharmacology
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Intracellular Signaling Peptides and Proteins
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Janus Kinase 3
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Mice
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Phosphoproteins / metabolism
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Phosphorylation
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Protein-Tyrosine Kinases / metabolism
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Receptors, Interleukin-4 / analysis
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STAT6 Transcription Factor
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Signal Transduction
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Th1 Cells / immunology*
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Th2 Cells / immunology
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Trans-Activators / metabolism
Substances
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Insulin Receptor Substrate Proteins
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Intracellular Signaling Peptides and Proteins
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Irs2 protein, mouse
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Phosphoproteins
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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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Trans-Activators
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Interleukin-4
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Protein-Tyrosine Kinases
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Jak3 protein, mouse
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Janus Kinase 3