A novel role for IL-3: human monocytes cultured in the presence of IL-3 and IL-4 differentiate into dendritic cells that produce less IL-12 and shift Th cell responses toward a Th2 cytokine pattern.
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.
Ebner
Susanne
S
Department of Dermatology and Internal Medicine, University of Innsbruck, Innsbruck, Austria. susanne.ebner@uibk.ac.at
Hofer
Susanne
S
Nguyen
Van Anh
VA
Fürhapter
Christina
C
Herold
Manfred
M
Fritsch
Peter
P
Heufler
Christine
C
Romani
Nikolaus
N
D000276:Adjuvants, Immunologic / Q000502:physiology; D000818:Animals; D018949:Antigens, CD1 / Q000096:biosynthesis; D023201:CD40 Ligand / Q000502:physiology; D002454:Cell Differentiation / Q000276:immunology; D048429:Cell Size / Q000276:immunology; D002478:Cells, Cultured; D018920:Coculture Techniques; D016207:Cytokines / Q000096:biosynthesis*; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D004306:Dose-Response Relationship, Immunologic; D015536:Down-Regulation / Q000276:immunology; D029721:Drosophila Proteins; D004338:Drug Combinations; D004705:Endocytosis / Q000276:immunology; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D006801:Humans; D016130:Immunophenotyping; D007371:Interferon-gamma / Q000096:biosynthesis; D007375:Interleukin-1 / Q000096:biosynthesis; D016753:Interleukin-10 / Q000096:biosynthesis; D018664:Interleukin-12 / Q000096:biosynthesis*; D007377:Interleukin-3 / Q000494:pharmacology*; D053650:Interleukin-3 Receptor alpha Subunit; D015847:Interleukin-4 / Q000096:biosynthesis / Q000494:pharmacology*; D015848:Interleukin-5 / Q000096:biosynthesis; D007958:Leukocyte Count; D007959:Lymphocyte Culture Test, Mixed; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000235:genetics; D051379:Mice; D009000:Monocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis; D011956:Receptors, Cell Surface / Q000096:biosynthesis / Q000235:genetics; D016187:Receptors, Granulocyte-Macrophage Colony-Stimulating Factor / Q000096:biosynthesis; D016185:Receptors, Interleukin-3 / Q000096:biosynthesis; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology* / Q000378:metabolism; D018418:Th2 Cells / Q000276:immunology* / Q000378:metabolism; D051193:Toll-Like Receptors; D014407:Tumor Cells, Cultured; D015854:Up-Regulation / Q000276:immunology
D000276:Adjuvants, Immunologic; D018949:Antigens, CD1; D016207:Cytokines; D029721:Drosophila Proteins; D004338:Drug Combinations; C115022:IL3RA protein, human; D007375:Interleukin-1; D007377:Interleukin-3; D053650:Interleukin-3 Receptor alpha Subunit; D015848:Interleukin-5; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D016187:Receptors, Granulocyte-Macrophage Colony-Stimulating Factor; D016185:Receptors, Interleukin-3; D051193:Toll-Like Receptors; D016753:Interleukin-10; D023201:CD40 Ligand; D018664:Interleukin-12; D015847:Interleukin-4; D007371:Interferon-gamma; D016178:Granulocyte-Macrophage Colony-Stimulating Factor