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Selective depletion of CD11c(+) CD11b(+) dendritic cells partially abrogates tolerogenic effects of intravenous MOG in murine EAE

Wang, L;Li, Z;Ciric, B;Safavi, F;Zhang, GX;Rostami, A;

Intravenous (i.v.) injection of a soluble myelin antigen can induce tolerance, which effectively ameliorates experimental autoimmune encephalomyelitis (EAE). We have previously shown that i.v. MOG induces tolerance in EAE and expands a subpopulation of tolerogenic CD11c(+) CD11b(+) dendritic cells (DCs) with an immature phenotype having low expression of IA and co-stimulatory molecules CD40, CD86, and CD80. Here we further investigate the role of tolerogenic DCs in i.v. tolerance by injecting clodronate-loaded liposomes, which selectively deplete CD11c(+) CD11b(+) and immature DCs, but not CD11c(+) CD8(+) DCs and mature DCs. I.v. MOG-induced suppression of EAE was partially, yet significantly, blocked by CD11c(+) CD11b(+) DC depletion. While i.v. MOG inhibited IA, CD40, CD80, CD86 expression and induced TGF-, IL-27, IL-10 production in CD11c(+) CD11b(+) DCs, these effects were abrogated after injection of clodronate-loaded liposomes. Depletion of CD11c(+) CD11b(+) DCs also precluded i.v. autoantigen-induced T-cell tolerance, such as decreased production of IL-2, IFN-, IL-17 and numbers of IL-2(+) , IFN-(+) , and IL-17(+) CD4(+) T cells, as well as an increased proportion of CD4(+) CD25(+) Foxp3(+) regulatory T cells and CD4(+) IL-10(+) Foxp3(-) Tr1 cells. CD11c(+) CD11b(+) DCs, through low expression of IA and co-stimulatory molecules as well as high expression of TGF-, IL-27 and IL-10, play an important role in i.v. tolerance-induced EAE suppression. This article is protected by copyright. All rights reserved.