title: Differentially modulated dendritic cells induce regulatory T cells with different characteristics.
abstract: Dexamethason (DEX) treated DC display several features that establish them as candidates for specific allogeneic tolerance induction. We report the results of in vitro studies of polarization of the alloimmune T cell response with two types of differentially modulated human DC. Both DEX treated DC triggered by LPS for 6 h (DEX6-DC) and DEX treated DC triggered by LPS for 48 h (DEX48-DC) acquired low levels of costimulatory, adhesion, and MHC class II molecules compared with mature DC (mDC). In contrast to mDC, both DEX6-DC and DEX48-DC did not produce any IL-12. DEX6-DC were able to produce significant amounts of IL-10 whereas DEX48-DC did not actively produce IL-10. Conversely, the induction of IL-10 producing cells was significantly increased when PBL were stimulated with DEX48-DC compared with DEX6-DC. Both stimulation of PBL with DEX6-DC and DEX48-DC led to the induction of cell populations able to suppress the proliferative alloimmune response of primed T cells in a cell-cell contact independent and antigen-nonspecific manner. Tregs obtained after stimulation with DEX48-DC were also able to inhibit the IFN-gamma production of the effector cells and this effect could be blocked by anti-IL-10. Tregs induced by DEX6-DC produced similar amounts of IL-10, yet were not able to inhibit IFN-gamma production of the effector T cells, indicating a different mechanism. In summary, we show that differential modulation of DC results in the induction of different populations of regulatory T cells.
authors.affiliation: Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, PO Box 9600, 2300 RC, Leiden, The Netherlands. D.L.Roelen@LUMC.nl
authors.forename: Dave L
authors.initials: DL
authors.lastname: Roelen
authors.forename: Daniëlle E M
authors.initials: DE
authors.lastname: van den Boogaardt
authors.forename: Paula P M C
authors.initials: PP
authors.lastname: van Miert
authors.forename: Karin
authors.initials: K
authors.lastname: Koekkoek
authors.forename: Rienk
authors.initials: R
authors.lastname: Offringa
authors.forename: Frans H J
authors.initials: FH
authors.lastname: Claas
mesh_terms: D017951:Antigen Presentation; D002450:Cell Communication / Q000187:drug effects / Q000276:immunology; D002454:Cell Differentiation / Q000187:drug effects / Q000276:immunology; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology*; D003907:Dexamethasone / Q000494:pharmacology; D006801:Humans; D007108:Immune Tolerance; D016130:Immunophenotyping; D008070:Lipopolysaccharides / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology*; D037182:T-Cell Antigen Receptor Specificity / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism
chemical_list: D016207:Cytokines; D008070:Lipopolysaccharides; C433788:lipopolysaccharide, E. coli O26-B6; D003907:Dexamethasone