CD11c+CD11b+ dendritic cells play an important role in intravenous tolerance and the suppression of experimental autoimmune encephalomyelitis.

Publication/Presentation Date

8-15-2008

Abstract

The central role of T cells in the induction of immunological tolerance against i.v. Ags has been well documented. However, the role of dendritic cells (DCs), the most potent APCs, in this process is not clear. In the present study, we addressed this issue by examining the involvement of two different DC subsets, CD11c(+)CD11b(+) and CD11c(+)CD8(+) DCs, in the induction of i.v. tolerance. We found that mice injected i.v. with an autoantigen peptide of myelin oligodendrocyte glycoprotein (MOG) developed less severe experimental autoimmune encephalomyelitis (EAE) following immunization with MOG peptide but presented with more CD11c(+)CD11b(+) DCs in the CNS and spleen. Upon coculturing with T cells or LPS, these DCs exhibited immunoregulatory characteristics, including increased production of IL-10 and TGF-beta but reduced IL-12 and NO; they were also capable of inhibiting the proliferation of MOG-specific T cells and enhancing the generation of Th2 cells and CD4(+)CD25(+)Foxp3(+) regulatory T cells. Furthermore, these DCs significantly suppressed ongoing EAE upon adoptive transfer. These results indicate that CD11c(+)CD11b(+) DCs, which are abundant in the CNS of tolerized animals, play a crucial role in i.v. tolerance and EAE and may be a candidate cell population for immunotherapy of autoimmune diseases.

Volume

181

Issue

4

First Page

2483

Last Page

2493

ISSN

1550-6606

Disciplines

Business Administration, Management, and Operations | Health and Medical Administration | Management Sciences and Quantitative Methods

PubMedID

18684939

Department(s)

Administration and Leadership

Document Type

Article

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