title: Immunomodulatory dendritic cells inhibit Th1 responses and arthritis via different mechanisms.
abstract: Dendritic cells (DCs) are professional APCs which have the unique ability to present both foreign and self-Ags to T cells and steer the outcome of immune responses. Because of these characteristics, DCs are attractive vehicles for the delivery of therapeutic vaccines. Fully matured DCs are relatively well-defined and even used in clinical trials in cancer. DCs also have the potential to influence the outcome of autoimmunity by modulating the underlying autoimmune response. To gain a better appreciation of the abilities and mechanisms by which immunomodulatory DCs influence the outcome of T cell responses, we studied several immunomodulatory DCs (TNF-, IL-10-, or dexamethasone-stimulated bone marrow-derived DCs) side by side for their ability to modulate T cell responses and autoimmune diseases. Our data show that these differentially modulated DCs display a different composition of molecules involved in T cell activation. Although, all DC subsets analyzed were able to inhibit the induction of collagen-induced arthritis, the modulation of the underlying immune response was different. Vaccination with TNF- or IL-10-modulated DCs altered the Th1/Th2 balance as evidenced by the induction of IL-5- and IL-10-secreting T cells and the concomitant reduction of the IgG2a-IgG1 ratio against the immunizing Ag. In contrast, DCs modulated with dexamethasone did not affect the ratio of IL-5-producing vs IFN-gamma-producing T cells and tended to affect the Ab response in a nonspecific manner. These data indicate that distinct mechanisms can be used by distinct DC subsets to change the outcome of autoimmunity.
authors.affiliation: Department of Rheumatology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Leonie M
authors.initials: LM
authors.lastname: van Duivenvoorde
authors.forename: Wanda G H
authors.initials: WG
authors.lastname: Han
authors.forename: Aleida M
authors.initials: AM
authors.lastname: Bakker
authors.forename: Pascale
authors.initials: P
authors.lastname: Louis-Plence
authors.forename: Louis-Marie
authors.initials: LM
authors.lastname: Charbonnier
authors.forename: Florence
authors.initials: F
authors.lastname: Apparailly
authors.forename: Ellen I H
authors.initials: EI
authors.lastname: van der Voort
authors.forename: Christian
authors.initials: C
authors.lastname: Jorgensen
authors.forename: Tom W J
authors.initials: TW
authors.lastname: Huizinga
authors.forename: René E M
authors.initials: RE
authors.lastname: Toes
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D001169:Arthritis, Experimental / Q000276:immunology* / Q000517:prevention & control*; D002478:Cells, Cultured; D024043:Collagen Type II / Q000008:administration & dosage / Q000276:immunology; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology* / Q000637:transplantation*; D003907:Dexamethasone / Q000494:pharmacology; D007108:Immune Tolerance / Q000187:drug effects; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008811:Mice, Inbred DBA; D008822:Mice, Transgenic; D018417:Th1 Cells / Q000276:immunology* / Q000378:metabolism
chemical_list: D024043:Collagen Type II; D003907:Dexamethasone