Alloantigen-presenting plasmacytoid dendritic cells mediate tolerance to vascularized grafts

Jordi C. Ochando; Chiho Homma; Yu Yang; Andres Hidalgo; Alexandre Garin; Frank Tacke; Veronique Angeli; Yansui Li; Peter Boros; Yaozhong Ding; Rolf Jessberger; Giorgio Trinchieri; Sergio A. Lira; Gwendalyn J. Randolph; Jonathan S. Bromberg

doi:10.1038/ni1333

Alloantigen-presenting plasmacytoid dendritic cells mediate tolerance to vascularized grafts

Jordi C. Ochando, Chiho Homma, Yu Yang, Andres Hidalgo, Alexandre Garin, Frank Tacke, Veronique Angeli, Yansui Li, Peter Boros, Yaozhong Ding, Rolf Jessberger, Giorgio Trinchieri, Sergio A. Lira, Gwendalyn J. Randolph, Jonathan S. Bromberg

Research output: Contribution to journal › Article › peer-review

564 Scopus citations

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.

Original language	English
Pages (from-to)	652-662
Number of pages	11
Journal	Nature Immunology
Volume	7
Issue number	6
DOIs	https://doi.org/10.1038/ni1333
State	Published - Jun 2006

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@article{62869838117b47bbbbbe3c60d19537fb,

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.",

author = "Ochando, {Jordi C.} and Chiho Homma and Yu Yang and Andres Hidalgo and Alexandre Garin and Frank Tacke and Veronique Angeli and Yansui Li and Peter Boros and Yaozhong Ding and Rolf Jessberger and Giorgio Trinchieri and Lira, {Sergio A.} and Randolph, {Gwendalyn J.} and Bromberg, {Jonathan S.}",

note = "Funding Information: We acknowledge the technical contributions of J. Llodra, H. Nikolayevskiy and S. Freeman, and discussions with M. Merad. Supported by National Institutes of Health (R01 AI41428, AI44929 and AI62765 to J.S.B.).",

year = "2006",

month = jun,

doi = "10.1038/ni1333",

language = "English",

volume = "7",

pages = "652--662",

journal = "Nature Immunology",

issn = "1529-2908",

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T1 - Alloantigen-presenting plasmacytoid dendritic cells mediate tolerance to vascularized grafts

AU - Ochando, Jordi C.

AU - Homma, Chiho

AU - Yang, Yu

AU - Hidalgo, Andres

AU - Garin, Alexandre

AU - Tacke, Frank

AU - Angeli, Veronique

AU - Li, Yansui

AU - Boros, Peter

AU - Ding, Yaozhong

AU - Jessberger, Rolf

AU - Trinchieri, Giorgio

AU - Lira, Sergio A.

AU - Randolph, Gwendalyn J.

AU - Bromberg, Jonathan S.

N1 - Funding Information: We acknowledge the technical contributions of J. Llodra, H. Nikolayevskiy and S. Freeman, and discussions with M. Merad. Supported by National Institutes of Health (R01 AI41428, AI44929 and AI62765 to J.S.B.).

PY - 2006/6

Y1 - 2006/6

N2 - 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.

AB - 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.

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JO - Nature Immunology

JF - Nature Immunology

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ER -

Alloantigen-presenting plasmacytoid dendritic cells mediate tolerance to vascularized grafts

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