Abstract
It is not known whether subsets of dendritic cells provide different cytokine microenvironments that determine the differentiation of either type-1 T helper (TH1) or TH2 cells. Human monocyte (pDC1)-derived dendritic cells (DC1) were found to induce TH1 differentiation, whereas dendritic cells (DC2) derived from CD4+CD3-CD11c- plasmacytoid cells (pDC2) induced TH2 differentiation by use of a mechanism unaffected by interleukin-4 (IL-4) or IL-12. The TH2 cytokine IL-4 enhanced DC1 maturation and killed pDC2, an effect potentiated by IL-10 but blocked by CD40 ligand and interferon-gamma. Thus, a negative feedback loop from the mature T helper cells may selectively inhibit prolonged TH1 or TH2 responses by regulating survival of the appropriate dendritic cell subset.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Apoptosis
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CD40 Antigens
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CD40 Ligand
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Cell Differentiation
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Cell Lineage
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Cell Survival
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Cells, Cultured
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Coculture Techniques
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Dendritic Cells / cytology*
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Dendritic Cells / immunology
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Feedback
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Humans
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Interferon-gamma / biosynthesis
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Interferon-gamma / pharmacology
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Interleukin-12 / biosynthesis
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Interleukin-12 / pharmacology
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Interleukin-12 / physiology
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Interleukin-4 / biosynthesis
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Interleukin-4 / pharmacology
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Interleukin-4 / physiology*
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Interleukins / biosynthesis
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Interleukins / pharmacology
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Lymphocyte Activation
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Membrane Glycoproteins / pharmacology
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Stem Cells / cytology
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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
Substances
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CD40 Antigens
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Interleukins
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Membrane Glycoproteins
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CD40 Ligand
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Interleukin-12
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Interleukin-4
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Interferon-gamma