Stromal cells direct local differentiation of regulatory dendritic cells.
CD11c(hi) dendritic cells (DC) play an essential role during the initiation of cell-mediated immunity. Recently, CD11c(lo)CD45RB(hi) DC with regulatory properties have been described. However, the origins of regulatory DC are poorly understood. Here, we show that spleen-derived stromal cells promote selective development of CD11c(lo)CD45RB(+) IL-10-producing regulatory DC from lineage-negative c-kit(+) progenitor cells. These DC have the capacity to suppress T cell responses and induce IL-10-producing regulatory T cells in vitro and to induce antigen-specific tolerance in vivo. Furthermore, stromal cells from mice infected with Leishmania donovani more effectively supported differentiation of these highly potent regulatory DC. The ability of tissue stromal cells to direct the development of DC with a regulatory phenotype thus provides a new mechanism for local immune regulation.
Svensson
Mattias
M
Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, Keppel Street, London WC1E 7HT, UK.
Maroof
Asher
A
Ato
Manabu
M
Kaye
Paul M
PM
D000818:Animals; D018845:CD11 Antigens / Q000276:immunology; D002454:Cell Differentiation; D003713:Dendritic Cells / Q000166:cytology* / Q000276:immunology*; D007108:Immune Tolerance / Q000276:immunology; D007891:Leishmania / Q000502:physiology; D007896:Leishmaniasis / Q000276:immunology / Q000469:parasitology; D017493:Leukocyte Common Antigens / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D017154:Stromal Cells / Q000502:physiology*
D018845:CD11 Antigens; D017493:Leukocyte Common Antigens