Oral dendritic cells mediate antigen-specific tolerance by stimulating T_H1 and regulatory CD4~+ T cells

摘要

Background: A detailed characterization of oral antigen-presenting cells is critical to improve second-generation sublingual allergy vaccines.Objective: To characterize oral dendritic cells (DCs) within lingual and buccal tissues from BALB/c mice with respect to their surface phenotype, distribution, and capacity to polarize CD4~+ T-cell responses.Methods: In situ analysis of oral DCs was performed by immunohistology. Purified DCs were tested in vitro for their capacity to capture, process, and present the ovalbumin antigen to naive CD4~+ T cells. In vivo priming of ovalbumin-specific T cells adoptively transferred to BALB/c mice was analyzed by cytofluorometry in cervical lymph nodes after sublingual administration of mucoadhesive ovalbumin.Results: Three subsets of oral DCs with a distinct tissue distribution were identified: (1) a minor subset of CD207~ Langerhans cells located in the mucosa itself, (2) a major subpopulation of CD11b~+CD11c~ and CD11b~+CD11c~+ myeloid DCs at the mucosal/submucosal interface, and (3) B220~+120G8~+ plasmacytoid DCs found in submucosal tissues. Purified myeloid and plasmacytoid oral DCs capture and process the antigen efficiently and are programmed to elicit IFN-7 and/or IL-10 production together with a suppressive function in naive CD4~+ T cells. Targeting the ovalbumin antigen to oral DCs in vivo by using mucoadhesive particles establishes tolerance in the absence of cell depletion through the stimulation of IFN-7 and IL-10-producing CD4~+ regulatory T cells in cervical lymph nodes