Immature dendritic cells suppress collagen-induced arthritis by in vivo expansion of CD49b+ regulatory T cells |
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Authors: | Charbonnier Louis-Marie van Duivenvoorde Leonie M Apparailly Florence Cantos Céline Han Wanda G H Noël Danièle Duperray Christophe Huizinga Tom W J Toes René E M Jorgensen Christian Louis-Plence Pascale |
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Institution: | Institut National de la Santé et de la Recherche Médicale Unité 475, Montpellier, France. |
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Abstract: | 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+ alpha-galactosylceramide/CD1d-nonrestricted T cell population producing IL-10. Adoptive transfer of < 10(5) TCRbeta+ 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. |
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