Dendritic cells differently respond to haptens and irritants by their production of cytokines and expression of co-stimulatory molecules.
After application of haptens to the skin, Langerhans cells (LC), i.e. immature dendritic cells (DC) in the skin, move to secondary lymphoid organs to sensitize naive T cells. During this process, LC become mature DC with augmented expression of various co-stimulatory molecules and MHC class II antigens. In this scenario, however, critical questions remain as to what kind of chemicals can induce this maturation process through what kind of mechanisms. To clarify these questions, we used monocyte-derived CD1a+ DC instead of LC since LC maturated spontaneously in vitro culture. After we confirmed that monocyte-derived DC showed at least phenotypic characteristics and a response to TNF-alpha similar to LC, we added various chemicals, i.e., dinitrochlorobenzene (DNCB), trinitrochlorobenzene (TNCB), NiCl2, ZnCl2, sodium dodecyl sulfate (SDS), or benzalkonium chloride (BC), to a culture of purified monocyte-derived CD1a+ DC. Of these chemicals, only NiCl2 and DNCB significantly increased the surface expression of CD54, CD86, HLA-DR antigen, and interleukin (IL)-1 beta production, while SDS, BC, or ZnCl2 could not augment them, except for weak augmentation of CD86 expression by SDS. The increase in the expression of CD86 induced by NiCl2 or DNCB was most remarkable, being observed in DC from almost all the subjects we examined. TNCB could also induce responses similar to those induced with DNCB, but the number of subjects whose DC responded to it was far less than that of subjects whose DC responded to NiCl2 or DNCB. In spite of the augmented CD86 expression on DC treated with DNCB or NiCl2, these chemicals induced different responses of DC in their expression of CD54 and HLA-DR and the production of IL-6 and tumor necrosis factor (TNF)-alpha. In addition, the up-regulation of CD86 expression on DC treated with DNCB was significantly suppressed by either anti-IL-1 beta or anti-TNF-alpha antibody, while that by NiCl2 was relatively insensitive to these antibody treatments. Finally, the protein kinase C inhibitor, H7, but not staurosporine, could suppress the augmentation of CD86 expression on DC induced either by NiCl2 or by DNCB. These data suggest that DC respond to some haptens by changing their expression of several co-stimulatory molecules and their production of cytokines with a resultant change in antigen-presenting function. They also suggest that these chemicals stimulate DC by different mechanisms. By these responses, DC may modulate the final immune response to chemicals.
Aiba
S
S
Department of Dermatology, Tohoku University School of Medicine, Aobaku, Japan. aiba@mail.cc.tohoku.ac.jp
Terunuma
A
A
Manome
H
H
Tagami
H
H
D000906:Antibodies / Q000494:pharmacology; D015703:Antigens, CD / Q000096:biosynthesis / Q000187:drug effects / Q000276:immunology; D051940:B7-2 Antigen; D001548:Benzalkonium Compounds / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects / Q000276:immunology; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis* / Q000187:drug effects / Q000276:immunology; D003713:Dendritic Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D004137:Dinitrochlorobenzene / Q000494:pharmacology; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D006241:Haptens / Q000276:immunology*; D006801:Humans; D016130:Immunophenotyping; D015847:Interleukin-4 / Q000494:pharmacology; D007509:Irritants / Q000494:pharmacology*; D007801:Langerhans Cells / Q000166:cytology; D018950:Lipopolysaccharide Receptors / Q000032:analysis; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000187:drug effects / Q000276:immunology; D019216:Metals, Heavy / Q000494:pharmacology; D009000:Monocytes / Q000166:cytology / Q000276:immunology; D010853:Picryl Chloride / Q000494:pharmacology; D011994:Recombinant Proteins / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects / Q000276:immunology; D012967:Sodium Dodecyl Sulfate / Q000494:pharmacology; D015854:Up-Regulation / Q000187:drug effects / Q000276:immunology
D000906:Antibodies; D015703:Antigens, CD; D051940:B7-2 Antigen; D001548:Benzalkonium Compounds; C497964:CD86 protein, human; D016207:Cytokines; D004137:Dinitrochlorobenzene; D006241:Haptens; D007509:Irritants; D018950:Lipopolysaccharide Receptors; D008562:Membrane Glycoproteins; D019216:Metals, Heavy; D011994:Recombinant Proteins; D015847:Interleukin-4; D012967:Sodium Dodecyl Sulfate; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D010853:Picryl Chloride