Plasmacytoid dendritic cells mediate oral tolerance.
Oral tolerance prevents oral sensitization to dietary antigens (Ags), including proteins and haptens, and development of delayed-type hypersensitivity (DTH) responses. We showed here that plasmacytoid dendritic cells (pDCs) prevented oral T cell priming and were responsible for systemic tolerance to CD4(+) and CD8(+) T cell-mediated DTH responses induced by Ag feeding. Systemic depletion of pDCs prevented induction of tolerance by antigen feeding. Transfer of oral Ag-loaded liver pDCs to naive recipient mice induced Ag-specific suppression of CD4(+) and CD8(+) T cell responses to protein and hapten, respectively. Liver is a site of oral Ag presentation, and pDCs appeared to induce anergy or deletion of Ag-specific T cells in the liver relatively rapidly via a CD4(+) T cell-independent mechanism. These data demonstrate that oral tolerance relies on Ag presentation by pDC to T cells and suggest that pDC could represent a key therapeutic target for intestinal and systemic inflammatory diseases.
Goubier
Anne
A
INSERM, U851, 21 Avenue Tony Garnier, Lyon F-69007, France.
Dubois
Bertrand
B
Gheit
Hanane
H
Joubert
Grégoire
G
Villard-Truc
Florence
F
Asselin-Paturel
Carine
C
Trinchieri
Giorgio
G
Kaiserlian
Dominique
D
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D004139:Dinitrofluorobenzene / Q000276:immunology; D005260:Female; D006968:Hypersensitivity, Delayed / Q000276:immunology* / Q000378:metabolism; D007108:Immune Tolerance; D008099:Liver / Q000276:immunology; D008198:Lymph Nodes / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D009061:Mouth Mucosa / Q000276:immunology*; D013154:Spleen / Q000276:immunology
D004139:Dinitrofluorobenzene
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