title: Antigen-specific effector CD4 T lymphocytes school lamina propria dendritic cells to transfer innate tolerance.
abstract: Dendritic cells (DCs) have been shown to play a major role in oral tolerance, and this function has been associated with their ability to produce anti-inflammatory cytokines and to induce suppressive regulatory T cells. In this study, we demonstrate that upon oral administration of Ag, lamina propia (LP) DCs engage specific T cells and acquire a novel mechanism by which they transfer tolerance against diverse T cell specificities. Indeed, when Ig-myelin oligodendrocyte glycoprotein (MOG) carrying the MOG(35-55) epitope was orally administered into either T cell-sufficient or -deficient mice, only the T cell-sufficient hosts yielded CD8α(+) and CD8α(-) LP DCs that were able to transfer tolerance to a variety of MHC class II-restricted effector T cells. Surprisingly, these LP DCs upregulated programmed cell death ligand 1 during the initial interaction with MOG-specific T cells and used this inhibitory molecule to suppress activation of T cells regardless of Ag specificity. Furthermore, oral Ig-MOG was able to overcome experimental autoimmune encephalomyelitis induced with CNS homogenate, indicating that the DCs are able to modulate disease involving diverse T cell specificities. This previously unrecognized attribute potentiates DCs against autoimmunity.
authors.affiliation: Department of Molecular Microbiology and Immunology, University of Missouri School of Medicine, Columbia, MO 65212, USA.
authors.forename: Jason A
authors.initials: JA
authors.lastname: Cascio
authors.forename: Cara L
authors.initials: CL
authors.lastname: Haymaker
authors.forename: Rohit D
authors.initials: RD
authors.lastname: Divekar
authors.forename: Sarah
authors.initials: S
authors.lastname: Zaghouani
authors.forename: Marie-Therese
authors.initials: MT
authors.lastname: Khairallah
authors.forename: Xiaoxiao
authors.initials: X
authors.lastname: Wan
authors.forename: Linda M
authors.initials: LM
authors.lastname: Rowland
authors.forename: Mermagya
authors.initials: M
authors.lastname: Dhakal
authors.forename: Weirong
authors.initials: W
authors.lastname: Chen
authors.forename: Habib
authors.initials: H
authors.lastname: Zaghouani
mesh_terms: D000284:Administration, Oral; D019264:Adoptive Transfer; D000818:Animals; D001324:Autoantigens / Q000276:immunology; D015551:Autoimmunity / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002469:Cell Separation; D003713:Dendritic Cells / Q000276:immunology*; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D007108:Immune Tolerance / Q000276:immunology*; D007113:Immunity, Innate / Q000276:immunology; D018928:Immunity, Mucosal / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009092:Mucous Membrane / Q000276:immunology*; D063308:Myelin-Oligodendrocyte Glycoprotein / Q000008:administration & dosage / Q000276:immunology; D010446:Peptide Fragments / Q000008:administration & dosage / Q000276:immunology
chemical_list: D001324:Autoantigens; D063308:Myelin-Oligodendrocyte Glycoprotein; D010446:Peptide Fragments; C445081:myelin oligodendrocyte glycoprotein (35-55)