title: Alloantigen-presenting plasmacytoid dendritic cells mediate tolerance to vascularized grafts.
abstract: The induction of alloantigen-specific unresponsiveness remains an elusive goal in organ transplantation. Here we identify plasmacytoid dendritic cells (pDCs) as phagocytic antigen-presenting cells essential for tolerance to vascularized cardiac allografts. Tolerizing pDCs acquired alloantigen in the allograft and then moved through the blood to home to peripheral lymph nodes. In the lymph node, alloantigen-presenting pDCs induced the generation of CCR4+ CD4+ CD25+ Foxp3+ regulatory T cells (Treg cells). Depletion of pDCs or prevention of pDC lymph node homing inhibited peripheral Treg cell development and tolerance induction, whereas adoptive transfer of tolerized pDCs induced Treg cell development and prolonged graft survival. Thus, alloantigen-presenting pDCs home to the lymph nodes in tolerogenic conditions, where they mediate alloantigen-specific Treg cell development and allograft tolerance.
authors.affiliation: Department of Gene and Cell Medicine, Mount Sinai School of Medicine, New York, New York 10029-6574, USA. jordi.ochando@mssm.edu
authors.forename: Jordi C
authors.initials: JC
authors.lastname: Ochando
authors.forename: Chiho
authors.initials: C
authors.lastname: Homma
authors.forename: Yu
authors.initials: Y
authors.lastname: Yang
authors.forename: Andres
authors.initials: A
authors.lastname: Hidalgo
authors.forename: Alexandre
authors.initials: A
authors.lastname: Garin
authors.forename: Frank
authors.initials: F
authors.lastname: Tacke
authors.forename: Veronique
authors.initials: V
authors.lastname: Angeli
authors.forename: Yansui
authors.initials: Y
authors.lastname: Li
authors.forename: Peter
authors.initials: P
authors.lastname: Boros
authors.forename: Yaozhong
authors.initials: Y
authors.lastname: Ding
authors.forename: Rolf
authors.initials: R
authors.lastname: Jessberger
authors.forename: Giorgio
authors.initials: G
authors.lastname: Trinchieri
authors.forename: Sergio A
authors.initials: SA
authors.lastname: Lira
authors.forename: Gwendalyn J
authors.initials: GJ
authors.lastname: Randolph
authors.forename: Jonathan S
authors.initials: JS
authors.lastname: Bromberg
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D017951:Antigen Presentation / Q000276:immunology; D001011:Aorta / Q000276:immunology / Q000637:transplantation; D003713:Dendritic Cells / Q000276:immunology*; D006085:Graft Survival / Q000276:immunology; D016027:Heart Transplantation / Q000276:immunology*; D007519:Isoantigens / Q000276:immunology*; D008198:Lymph Nodes / Q000166:cytology / Q000276:immunology; D051379:Mice; D008815:Mice, Inbred Strains; D010587:Phagocytosis / Q000276:immunology; D011651:Pulmonary Artery / Q000276:immunology / Q000637:transplantation; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D023001:Transplantation Tolerance / Q000276:immunology*
chemical_list: D007519:Isoantigens