Cyclosporin A inhibits dendritic cell maturation promoted by TNF-alpha or LPS but not by double-stranded RNA or CD40L.
Here, we investigated the influence of cyclosporin A (CsA) on dendritic cell (DC) generation. With this aim, human DC were propagated from monocytes in serum-free medium with granulocyte macrophage-colony stimulating factor and interleukin-4. DC were then exposed to tumor necrosis factor alpha (TNF-alpha) for maturation. Our results show that CsA does not impair commitment of monocytes into DC, as assessed by loss of CD14 and increase of CD40 and CD1a. However, TNF-alpha-induced DC maturation was affected, as CsA-treated DC expressed lower levels of human leukocyte antigen and costimulatory molecules but sustained levels of CD1a, and less DC expressed DC-lysosomal-associated-membrane-protein (LAMP) and CD83. Accordingly, CsA inhibited the allostimulatory and accessory cell functions of DC. Surprisingly, when other maturation stimuli were used, we observed that CsA significantly inhibited maturation induced by lipopolysaccharides but not by polyribocytidylic acid or CD40 ligand, as assessed by DC phenotype and functions. Therefore, our results indicate that CsA may differentially affect DC maturation.
Duperrier
K
K
Department of Cell Therapy, HLA Clinical Pharmacology, Etablissement Français du Sang région Rhone-Alpes, site de Lyon, Centre Hospitalier Lyon-Sud, and Hopital Debrousse, France.
Farre
A
A
Bienvenu
J
J
Bleyzac
N
N
Bernaud
J
J
Gebuhrer
L
L
Rigal
D
D
Eljaafari
A
A
D017951:Antigen Presentation / Q000187:drug effects; D015703:Antigens, CD / Q000032:analysis; D023201:CD40 Ligand / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D016572:Cyclosporine / Q000494:pharmacology*; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology*; D004305:Dose-Response Relationship, Drug; D006684:HLA-DR Antigens / Q000032:analysis; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D007700:Kinetics; D008070:Lipopolysaccharides / Q000037:antagonists & inhibitors; D007959:Lymphocyte Culture Test, Mixed; D011070:Poly I-C / Q000037:antagonists & inhibitors; D012330:RNA, Double-Stranded / Q000037:antagonists & inhibitors; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors
D015703:Antigens, CD; D006684:HLA-DR Antigens; D007166:Immunosuppressive Agents; D008070:Lipopolysaccharides; D012330:RNA, Double-Stranded; D014409:Tumor Necrosis Factor-alpha; D023201:CD40 Ligand; D016572:Cyclosporine; D011070:Poly I-C