Abstract
Dendritic cells (DC) derived from plasmacytoid precursors depend on IL-3 for survival and proliferation in culture, and they induce preferentially Th2 responses. Monocytes express not only GM-CSF receptors, but also IL-3Rs. Therefore, we examined whether IL-3 had an effect on the functional plasticity of human monocyte-derived DC generated in a cell culture system that is widely used in immunotherapy. DC were generated with IL-3 (instead of GM-CSF) and IL-4. Yields, maturation, phenotype (surface markers and Toll-like receptors), morphology, and immunostimulatory capacity were similar. Only CD1a was differentially expressed, being absent on IL-3-treated DC. In response to CD40 ligation DC generated in the presence of IL-3 secreted significantly less IL-12 p70 and more IL-10 compared with DC grown with GM-CSF. Coculture of naive allogeneic CD4(+) T cells with DC generated in the presence of IL-3 induced T cells to produce significantly more IL-5 and IL-4 and less IFN-gamma compared with stimulation with DC generated with GM-CSF. These data extend the evidence that different cytokine environments during differentiation of monocyte-derived DC can modify their Th cell-inducing properties. A hitherto unrecognized effect of IL-3 on DC was defined, namely suppression of IL-12 secretion and a resulting shift from Th1 toward Th2.
MeSH terms
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Adjuvants, Immunologic / physiology
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Animals
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Antigens, CD1 / biosynthesis
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CD40 Ligand / physiology
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Cell Differentiation / immunology
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Cell Size / immunology
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Cells, Cultured
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Coculture Techniques
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Cytokines / biosynthesis*
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Dendritic Cells / cytology
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Dendritic Cells / immunology*
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Dendritic Cells / metabolism
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Dose-Response Relationship, Immunologic
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Down-Regulation / immunology
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Drosophila Proteins*
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Drug Combinations
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Endocytosis / immunology
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Granulocyte-Macrophage Colony-Stimulating Factor / pharmacology
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Humans
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Immunophenotyping
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Interferon-gamma / biosynthesis
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Interleukin-1 / biosynthesis
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Interleukin-10 / biosynthesis
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Interleukin-12 / biosynthesis*
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Interleukin-3 / pharmacology*
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Interleukin-3 Receptor alpha Subunit
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Interleukin-4 / biosynthesis
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Interleukin-4 / pharmacology*
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Interleukin-5 / biosynthesis
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Leukocyte Count
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Lymphocyte Culture Test, Mixed
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Membrane Glycoproteins / biosynthesis
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Membrane Glycoproteins / genetics
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Mice
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Monocytes / cytology
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Monocytes / immunology*
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Monocytes / metabolism
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RNA, Messenger / biosynthesis
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Receptors, Cell Surface / biosynthesis
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Receptors, Cell Surface / genetics
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Receptors, Granulocyte-Macrophage Colony-Stimulating Factor / biosynthesis
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Receptors, Interleukin-3 / biosynthesis
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T-Lymphocytes, Helper-Inducer / immunology*
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T-Lymphocytes, Helper-Inducer / metabolism
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Th2 Cells / immunology*
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Th2 Cells / metabolism
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Toll-Like Receptors
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Tumor Cells, Cultured
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Up-Regulation / immunology
Substances
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Adjuvants, Immunologic
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Antigens, CD1
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Cytokines
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Drosophila Proteins
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Drug Combinations
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IL3RA protein, human
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Interleukin-1
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Interleukin-3
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Interleukin-3 Receptor alpha Subunit
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Interleukin-5
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Membrane Glycoproteins
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RNA, Messenger
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Receptors, Cell Surface
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Receptors, Granulocyte-Macrophage Colony-Stimulating Factor
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Receptors, Interleukin-3
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Toll-Like Receptors
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Interleukin-10
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CD40 Ligand
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Interleukin-12
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Interleukin-4
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Interferon-gamma
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Granulocyte-Macrophage Colony-Stimulating Factor