Abstract
TGF-beta 1 is critical for differentiation of epithelial-associated dendritic Langerhans cells (LC). In accordance with the characteristics of in vivo LC, we show that LC obtained from human monocytes in vitro in the presence of TGF-beta 1 1) express almost exclusively intracellular class II Ags, low CD80, and no CD83 and CD86 Ags and 2) down-regulate TNF-RI (p55) and do not produce IL-10 after stimulation, in contrast to dermal dendritic cells and monocyte-derived dendritic cells. Surprisingly, while LC exhibit E-cadherin down-regulation upon exposure to TNF-alpha and IL-1, TGF-beta 1 prevents the final LC maturation in response to TNF-alpha, IL-1, and LPS with respect to Class II CD80, CD86, and CD83 Ag expression, loss of FITC-dextran uptake, production of IL-12, and Ag presentation. In sharp contrast, CD40 ligand cognate signal induces full maturation of LC and is not inhibited by TGF-beta 1. The presence of emigrated immature LCs in human reactive skin-draining lymph nodes provides in vivo evidence that LC migration and final maturation may be differentially regulated. Therefore, due to the effects of TGF-beta 1, inflammatory stimuli may not be sufficient to induce full maturation of LC, thus avoiding potentially harmful immune responses. We conclude that TGF-beta 1 appears to be responsible for both the acquisition of LC phenotype, cytokine production pattern, and prevention of noncognate maturation.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Antigens, CD / biosynthesis
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Antigens, CD / chemistry
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CD40 Antigens / metabolism
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CD40 Ligand
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Cell Differentiation / immunology
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Cell Movement / immunology
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Cells, Cultured
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Down-Regulation / immunology
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Growth Inhibitors / physiology*
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Humans
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Immunophenotyping
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Interleukin-1 / antagonists & inhibitors
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Interleukin-1 / pharmacology
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Interleukin-10 / antagonists & inhibitors
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Interleukin-10 / biosynthesis
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Interleukin-12 / antagonists & inhibitors
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Interleukin-12 / biosynthesis
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Langerhans Cells / cytology*
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Langerhans Cells / immunology*
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Langerhans Cells / metabolism
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Ligands
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Lipopolysaccharides / antagonists & inhibitors
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Lipopolysaccharides / pharmacology
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Lymphocyte Activation / immunology
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Membrane Glycoproteins / physiology
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Monocytes / cytology
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Monocytes / immunology
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Pinocytosis / immunology
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Receptors, Tumor Necrosis Factor / biosynthesis
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Receptors, Tumor Necrosis Factor / chemistry
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Receptors, Tumor Necrosis Factor, Type I
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T-Lymphocytes / immunology
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Tetanus Toxin / pharmacology
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Transforming Growth Factor beta / physiology*
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Tumor Necrosis Factor-alpha / antagonists & inhibitors
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Tumor Necrosis Factor-alpha / pharmacology
Substances
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Antigens, CD
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CD40 Antigens
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Growth Inhibitors
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Interleukin-1
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Ligands
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Lipopolysaccharides
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Membrane Glycoproteins
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Receptors, Tumor Necrosis Factor
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Receptors, Tumor Necrosis Factor, Type I
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Tetanus Toxin
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Transforming Growth Factor beta
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Tumor Necrosis Factor-alpha
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Interleukin-10
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CD40 Ligand
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Interleukin-12