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* Department of Rheumatology, Leiden University Medical Center, Leiden, The Netherlands;
Institut National de la Santé et de la Recherche Médicale Unité 844, Montpellier, France;
Centre Hospitalier Régional Universitaire Hôpital Lapeyronie, Unité Clinique d’Immuno-Rhumatologie, Thérapeutique des Maladies Articulaires et Osseuses, Montpellier, France; and
Université Montpellier 1, Unité de Formation et de Recherche de Médecine, Montpellier, France
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-
-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.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 This work was supported by the Dutch Arthritis Association (Projects 01-2-401 and 02-1-402), The Netherlands Organization for Scientific Research (VIDI Grant (to R.E.M.T.)), and European Community Framework Programme funding, Project 018661 Autocure.
2 L.M.v.D. and W.G.H.H. contributed equally to this work.
3 Address correspondence and reprint requests to Dr. René E. M. Toes, Department of Rheumatology, Leiden University Medical Center, P.O. Box 9600, 2333 ZA Leiden, The Netherlands. E-mail address: R.E.M.Toes{at}LUMC.nl
4 Abbreviations used in this paper: DC, dendritic cell; CIA, collagen-induced arthritis; RA, rheumatoid arthritis; CII, type II collagen; Dex, dexamethasone; PBA, PBS containing 0.5% BSA, 0.02% azide; PBA-sap, PBA containing 0.1% saponin; HA, influenza virus A; Treg, regulatory T cell; ACPA, Ab against citrullinated protein.
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