TGF-beta 1 prevents the noncognate maturation of human dendritic Langerhans cells.
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.
Geissmann
F
F
Unité de Recherche Associée 1461, Centre National de la Recherche Scientifique, Institut National de la Santé et de la Recherche Médicale, Unité 429, Paris, France. geissman@necker.fr
Revy
P
P
Regnault
A
A
Lepelletier
Y
Y
Dy
M
M
Brousse
N
N
Amigorena
S
S
Hermine
O
O
Durandy
A
A
D015703:Antigens, CD / Q000096:biosynthesis / Q000737:chemistry; D019013:CD40 Antigens / Q000378:metabolism; D023201:CD40 Ligand; D002454:Cell Differentiation / Q000276:immunology; D002465:Cell Movement / Q000276:immunology; D002478:Cells, Cultured; D015536:Down-Regulation / Q000276:immunology; D006131:Growth Inhibitors / Q000502:physiology*; D006801:Humans; D016130:Immunophenotyping; D007375:Interleukin-1 / Q000037:antagonists & inhibitors / Q000494:pharmacology; D016753:Interleukin-10 / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D018664:Interleukin-12 / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D007801:Langerhans Cells / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism; D008024:Ligands; D008070:Lipopolysaccharides / Q000037:antagonists & inhibitors / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000276:immunology; D008562:Membrane Glycoproteins / Q000502:physiology; D009000:Monocytes / Q000166:cytology / Q000276:immunology; D010873:Pinocytosis / Q000276:immunology; D018124:Receptors, Tumor Necrosis Factor / Q000096:biosynthesis / Q000737:chemistry; D047888:Receptors, Tumor Necrosis Factor, Type I; D013601:T-Lymphocytes / Q000276:immunology; D013744:Tetanus Toxin / Q000494:pharmacology; D016212:Transforming Growth Factor beta / Q000502:physiology*; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000494:pharmacology
D015703:Antigens, CD; D019013:CD40 Antigens; D006131:Growth Inhibitors; D007375:Interleukin-1; D008024:Ligands; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; D018124:Receptors, Tumor Necrosis Factor; D047888:Receptors, Tumor Necrosis Factor, Type I; D013744:Tetanus Toxin; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D023201:CD40 Ligand; D018664:Interleukin-12