Alloantigen-presenting plasmacytoid dendritic cells mediate tolerance to vascularized grafts

Publikation: Beitrag in FachzeitschriftForschungsartikelBeigetragenBegutachtung

Beitragende

  • Jordi C Ochando - , Icahn School of Medicine at Mount Sinai (Autor:in)
  • Chiho Homma - (Autor:in)
  • Yu Yang - (Autor:in)
  • Andres Hidalgo - (Autor:in)
  • Alexandre Garin - (Autor:in)
  • Frank Tacke - (Autor:in)
  • Veronique Angeli - (Autor:in)
  • Yansui Li - (Autor:in)
  • Peter Boros - (Autor:in)
  • Yaozhong Ding - (Autor:in)
  • Rolf Jessberger - , Institut für Physiologische Chemie, Icahn School of Medicine at Mount Sinai (Autor:in)
  • Giorgio Trinchieri - (Autor:in)
  • Sergio A Lira - (Autor:in)
  • Gwendalyn J Randolph - (Autor:in)
  • Jonathan S Bromberg - (Autor:in)

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.

Details

OriginalspracheEnglisch
Seiten (von - bis)652-662
Seitenumfang11
FachzeitschriftNature Immunology
Jahrgang7
Ausgabenummer6
PublikationsstatusVeröffentlicht - Juni 2006
Peer-Review-StatusJa

Externe IDs

Scopus 33744479421
PubMed 16633346

Schlagworte

Schlagwörter

  • Adoptive Transfer, Animals, Antigen Presentation/immunology, Aorta/immunology, Dendritic Cells/immunology, Graft Survival/immunology, Heart Transplantation/immunology, Isoantigens/immunology, Lymph Nodes/cytology, Mice, Mice, Inbred Strains, Phagocytosis/immunology, Pulmonary Artery/immunology, T-Lymphocytes, Regulatory/immunology, Transplantation Tolerance/immunology