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 (T_reg cells). Depletion of pDCs or prevention of pDC lymph node homing inhibited peripheral T_reg cell development and tolerance induction, whereas adoptive transfer of tolerized pDCs induced T_reg cell development and prolonged graft survival. Thus, alloantigen-presenting pDCs home to the lymph nodes in tolerogenic conditions, where they mediate alloantigen-specific T_reg cell development and allograft tolerance.