Journal of Leukocyte Biology
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(Journal of Leukocyte Biology. 2002;72:953-961.)
© 2002 by Society for Leukocyte Biology

Cyclosporin A inhibits dendritic cell maturation promoted by TNF-{alpha} or LPS but not by double-stranded RNA or CD40L

K. Duperrier, A. Farre, J. Bienvenu, N. Bleyzac, J. Bernaud, L. Gebuhrer, D. Rigal and A. Eljaafari

Departments of Cell Therapy, Immunology, HLA Clinical Pharmacology, Etablissement Français du Sang région Rhone-Alpes, site de Lyon, Centre Hospitalier Lyon-Sud, and Hopital Debrousse, France, Jeune equipe universitaire, 2267, UCLB, France

Correspondence: Dr. Assia Eljaafari, M.D., Ph.D., Banque de Tissus et Cellules, Pavillon I, Hôpital Edouard Herriot, 5 Place d’Arsonval, 69003 Lyon, France. E-mail: assia.eljaafari{at}efs.sante.fr

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.

Key Words: differential effect • immunosuppressive drug • antigen presenting cell function • accessory cell function • environmental stimulus




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