Immature dendritic cells suppress collagen-induced arthritis by in vivo expansion of CD49b+ regulatory T cells.
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.
Charbonnier
Louis-Marie
LM
Institut National de la Santé et de la Recherche Médicale Unité 475, Montpellier, France.
van Duivenvoorde
Leonie M
LM
Apparailly
Florence
F
Cantos
Céline
C
Han
Wanda G H
WG
Noël
Danièle
D
Duperray
Christophe
C
Huizinga
Tom W J
TW
Toes
René E M
RE
Jorgensen
Christian
C
Louis-Plence
Pascale
P
D019264:Adoptive Transfer; D000818:Animals; D001169:Arthritis, Experimental / Q000276:immunology* / Q000473:pathology / Q000517:prevention & control*; D016175:B-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D002454:Cell Differentiation / Q000276:immunology; D049109:Cell Proliferation; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000166:cytology* / Q000276:immunology* / Q000637:transplantation; D007274:Injections, Intraperitoneal; D039421:Integrin alpha2 / Q000096:biosynthesis*; D016753:Interleukin-10 / Q000096:biosynthesis / Q000378:metabolism; D008198:Lymph Nodes / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*
D039421:Integrin alpha2; D016753:Interleukin-10