Selective effects of cyclosporine a on Th2-skewed dendritic cells matured with viral-like stimulus by means of toll-like receptors.
Successful prevention of allograft rejection and graft-versus-host disease with immunosuppression depends on controlled balance of Th1 and Th2 immune responses to establish tolerance and fight infection. Here, we have analyzed the effects of cyclosporine A (CsA) on the differentiation and functions of dendritic cells (DC2) that induce Th2 T cells. DC2 were differentiated from monocytes in the presence of CsA and were matured with viral or bacterial agonists (poly[I:C] or lipopolysaccharide). DC2 differentiation was not affected by CsA. In contrast, cytokine responses were altered with inhibition of interleukin-10 production in poly(I:C)-matured DC2. Surprisingly, interleukin-10 secretion by immature DC2 was increased after CsA treatment. Internalization was impaired in treated DC2, and CsA decreased the T-cell proliferative capacity of DC2 matured with poly(I:C), but not with lipopolysaccharide. In conclusion, CsA altered T-cell activating functions of DC2 with, notably, a regulatory phenotype for immature DC2 and opposite effects on poly(I:C)-matured cells.
Abdul
Mubashira
M
INSERM U662, and Institut Universitaire d'Hématologie, Université Paris VII, Paris, France.
Charron
Dominique
D
Haziot
Alain
A
D002454:Cell Differentiation / Q000187:drug effects / Q000276:immunology; D016572:Cyclosporine / Q000494:pharmacology*; D016207:Cytokines / Q000502:physiology; D003713:Dendritic Cells / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology; D015847:Interleukin-4 / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D011070:Poly I-C / Q000494:pharmacology; D018418:Th2 Cells / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D051193:Toll-Like Receptors / Q000276:immunology*
D016207:Cytokines; D007166:Immunosuppressive Agents; D008070:Lipopolysaccharides; D051193:Toll-Like Receptors; D015847:Interleukin-4; D016572:Cyclosporine; D011070:Poly I-C