title: MHC class II-restricted antigen presentation by plasmacytoid dendritic cells inhibits T cell-mediated autoimmunity.
abstract: Although plasmacytoid dendritic cells (pDCs) express major histocompatibility complex class II (MHCII) molecules, and can capture, process, and present antigens (Ags), direct demonstrations that they function as professional Ag-presenting cells (APCs) in vivo during ongoing immune responses remain lacking. We demonstrate that mice exhibiting a selective abrogation of MHCII expression by pDCs develop exacerbated experimental autoimmune encephalomyelitis (EAE) as a consequence of enhanced priming of encephalitogenic CD4(+) T cell responses in secondary lymphoid tissues. After EAE induction, pDCs are recruited to lymph nodes and establish MHCII-dependent myelin-Ag-specific contacts with CD4(+) T cells. These interactions promote the selective expansion of myelin-Ag-specific natural regulatory T cells that dampen the autoimmune T cell response. pDCs thus function as APCs during the course of EAE and confer a natural protection against autoimmune disease development that is mediated directly by their ability to present of Ags to CD4(+) T cells in vivo.
authors.affiliation: Department of Pathology, University of Geneva Medical School, 1211 Geneva, Switzerland.
authors.forename: Magali
authors.initials: M
authors.lastname: Irla
authors.forename: Natalia
authors.initials: N
authors.lastname: Küpfer
authors.forename: Tobias
authors.initials: T
authors.lastname: Suter
authors.forename: Rami
authors.initials: R
authors.lastname: Lissilaa
authors.forename: Mahdia
authors.initials: M
authors.lastname: Benkhoucha
authors.forename: Jonathan
authors.initials: J
authors.lastname: Skupsky
authors.forename: Patrice H
authors.initials: PH
authors.lastname: Lalive
authors.forename: Adriano
authors.initials: A
authors.lastname: Fontana
authors.forename: Walter
authors.initials: W
authors.lastname: Reith
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Hugues
mesh_terms: D000818:Animals; D017951:Antigen Presentation; D015551:Autoimmunity; D001402:B-Lymphocytes / Q000276:immunology; D002454:Cell Differentiation; D049109:Cell Proliferation; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology*; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology*
chemical_list: D000949:Histocompatibility Antigens Class II