Immunomodulatory dendritic cells inhibit Th1 responses and arthritis via different mechanisms.
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.
van Duivenvoorde
Leonie M
LM
Department of Rheumatology, Leiden University Medical Center, Leiden, The Netherlands.
Han
Wanda G H
WG
Bakker
Aleida M
AM
Louis-Plence
Pascale
P
Charbonnier
Louis-Marie
LM
Apparailly
Florence
F
van der Voort
Ellen I H
EI
Jorgensen
Christian
C
Huizinga
Tom W J
TW
Toes
René E M
RE
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
D024043:Collagen Type II; D003907:Dexamethasone