title: Plasmacytoid dendritic cells mediate oral tolerance.
abstract: 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.
authors.affiliation: INSERM, U851, 21 Avenue Tony Garnier, Lyon F-69007, France.
authors.forename: Anne
authors.initials: A
authors.lastname: Goubier
authors.forename: Bertrand
authors.initials: B
authors.lastname: Dubois
authors.forename: Hanane
authors.initials: H
authors.lastname: Gheit
authors.forename: Grégoire
authors.initials: G
authors.lastname: Joubert
authors.forename: Florence
authors.initials: F
authors.lastname: Villard-Truc
authors.forename: Carine
authors.initials: C
authors.lastname: Asselin-Paturel
authors.forename: Giorgio
authors.initials: G
authors.lastname: Trinchieri
authors.forename: Dominique
authors.initials: D
authors.lastname: Kaiserlian
mesh_terms: 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
chemical_list: D004139:Dinitrofluorobenzene
references.citation: Nat Immunol. 2003 Apr;4(4):355-60
references.pmid: 12640450
references.citation: Nat Immunol. 2006 Jun;7(6):652-62
references.pmid: 16633346
references.citation: J Immunol. 1998 Feb 1;160(3):1181-90
references.pmid: 9570532
references.citation: Nat Rev Immunol. 2003 Jan;3(1):51-62
references.pmid: 12511875
references.citation: Am J Transplant. 2004 Oct;4(10):1574-82
references.pmid: 15367212
references.citation: J Immunol. 2000 Mar 1;164(5):2515-22
references.pmid: 10679089
references.citation: Immunity. 2006 Feb;24(2):191-201
references.pmid: 16473831
references.citation: Immunity. 2004 Sep;21(3):367-77
references.pmid: 15357948
references.citation: Annu Rev Immunol. 2004;22:531-62
references.pmid: 15032588
references.citation: J Immunol. 2003 Mar 1;170(5):2323-30
references.pmid: 12594254
references.citation: Immunology. 2003 Apr;108(4):481-92
references.pmid: 12667210
references.citation: Hepatology. 2003 Aug;38(2):403-12
references.pmid: 12883484
references.citation: J Pediatr Surg. 1994 Aug;29(8):1145-8
references.pmid: 7965523
references.citation: J Exp Med. 2004 Jul 5;200(1):89-98
references.pmid: 15238608
references.citation: J Immunol. 1998 Jun 15;160(12):5815-25
references.pmid: 9637492
references.citation: J Immunol. 2001 Jul 1;167(1):188-95
references.pmid: 11418648
references.citation: J Immunol. 1994 May 1;152(9):4663-70
references.pmid: 8157979
references.citation: J Immunol. 2001 Jun 15;166(12):7042-52
references.pmid: 11390448
references.citation: J Exp Med. 2007 Aug 6;204(8):1775-85
references.pmid: 17620362
references.citation: Immunity. 1998 Jun;8(6):667-73
references.pmid: 9655480
references.citation: J Clin Invest. 2007 Sep;117(9):2570-82
references.pmid: 17710230
references.citation: Eur J Immunol. 2003 May;33(5):1292-301
references.pmid: 12731054
references.citation: J Immunol. 2007 Sep 1;179(5):2690-4
references.pmid: 17709480
references.citation: Immunol Rev. 2005 Aug;206:232-59
references.pmid: 16048553
references.citation: J Clin Invest. 2004 Jul;114(2):280-90
references.pmid: 15254595
references.citation: Nature. 1967 Aug 12;215(5102):744-5
references.pmid: 6059543
references.citation: J Exp Med. 1999 Mar 1;189(5):779-86
references.pmid: 10049941
references.citation: J Exp Med. 2002 Apr 1;195(7):953-8
references.pmid: 11927638
references.citation: Gastroenterology. 2006 Aug;131(2):485-96
references.pmid: 16890603
references.citation: Nat Immunol. 2001 Dec;2(12):1144-50
references.pmid: 11713464
references.citation: Chem Res Toxicol. 2001 Sep;14(9):1209-17
references.pmid: 11559035
references.citation: J Exp Med. 2003 Jan 6;197(1):101-9
references.pmid: 12515817
references.citation: Eur J Immunol. 2001 Apr;31(4):1278-87
references.pmid: 11298355
references.citation: J Immunol. 2006 Sep 1;177(5):3260-5
references.pmid: 16920966
references.citation: Blood. 2002 Jul 15;100(2):383-90
references.pmid: 12091326
references.citation: Nat Rev Immunol. 2003 Apr;3(4):331-41
references.pmid: 12669023
references.citation: Cell Mol Life Sci. 2005 Jun;62(12):1322-32
references.pmid: 15971107
references.citation: J Immunol. 2001 Oct 15;167(8):4245-53
references.pmid: 11591746
references.citation: J Immunol. 2003 Dec 15;171(12):6466-77
references.pmid: 14662846
references.citation: Gut. 1979 Feb;20(2):121-5
references.pmid: 428823
references.citation: J Exp Med. 2007 Aug 6;204(8):1757-64
references.pmid: 17620361
references.citation: Blood. 2003 Nov 1;102(9):3295-301
references.pmid: 12855551
references.citation: Hepatology. 2007 Feb;45(2):445-54
references.pmid: 17256750
references.citation: J Exp Med. 2006 Mar 20;203(3):519-27
references.pmid: 16533884