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* Institut National de la Santé et de la Recherche Médicale Unité 475, Montpellier, France;
Department of Rheumatology, Leiden University Medical Centre, Leiden, The Netherlands;
Centre Hospitalier Universitaire Hôpital Lapeyronie, Unité Clinique d’Immuno-Rhumatologie, Thérapeutique des Maladies Articulaires et Osseuses, Montpellier, France; and
Université Montpellier 1, Montpellier, France
Dendritic cells (DCs) are specialized APCs with an important role in the initiation and regulation of immune responses. Immature DCs (iDCs) reportedly mediate tolerance in the absence of maturation/inflammatory stimuli, presumably by the induction of regulatory T cells. In this study, we show for the first time that repetitive iDC injections trigger the expansion of a novel regulatory population with high immunomodulatory properties, able to protect mice from collagen-induced arthritis. These regulatory T cells are characterized by the expression of the CD49b molecule and correspond to a CD4+ 
-galactosylceramide/CD1d-nonrestricted T cell population producing IL-10. Adoptive transfer of <105 TCR
+CD49b+ cells isolated from the liver of iDCs-vaccinated mice, conferred a complete protection against arthritis. This protection was associated with an attenuation of the B and T cell response associated with a local secretion of IL-10. Thus, together these data demonstrate that iDCs can expand and activate a novel regulatory population of CD49b+ T cells, with high immunosuppressive potential able to mediate protection against a systemic autoimmune disease.
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 in part by research funding from La Fondation de l’Avenir, the European Community’s FP6 funding Project 018661 Autocure, institutional funds from Institut National de la Santé et de la Recherche Médicale (to C.J.), the Dutch Arthritis Foundation, and the Dutch Organisation for Scientific Research Netherlands Organization for Scientific Research VIDI innovation grant (to R.E.M.T.). L.-M.C. was supported by Association de Recherche sur la Polyarthrite.
2 L.-M.C. and L.M.v.D. contributed equally to this work.
3 Address correspondence and reprint requests to Dr. Pascale Louis-Plence, Institut National de la Santé et de la Recherche Médicale Unité 475, 99 rue Puech Villa, 34197 Montpellier cedex 05, France. E-mail address: plence{at}montp.inserm.fr
4 Abbreviations used in this paper: DC, dendritic cell; RA, rheumatoid arthritis; iDC, immature DC; mDC, mature DC; EAE, experimental allergic encephalomyelitis; bCII, bovine collagen type II; CIA, collagen-induced arthritis; -GalCer, -galactosylceramide; ICS, intracellular cytokine staining; PPD, purified protein derivative; LPS-DC, LPS-treated DC.
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