Tolerogenic Donor-Derived Dendritic Cells Risk Sensitization In Vivo owing to Processing and Presentation by Recipient APCs

Lesley A. Smyth; Kulachelvy Ratnasothy; Aurelie Moreau; Sally Alcock; Pervinder Sagoo; Lucy Meader; Yakup Tanriver; Matthew Buckland; Robert Lechler; Giovanna Lombardi

doi:10.4049/jimmunol.1200870

Tolerogenic Donor-Derived Dendritic Cells Risk Sensitization In Vivo owing to Processing and Presentation by Recipient APCs

Lesley A. Smyth, Kulachelvy Ratnasothy, Aurelie Moreau, Sally Alcock, Pervinder Sagoo, Lucy Meader, Yakup Tanriver, Matthew Buckland, Robert Lechler, Giovanna Lombardi^*

^*Corresponding author for this work

King's College London

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

29 Citations (Scopus)

Abstract

Modification of allogeneic dendritic cells (DCs) through drug treatment results in DCs with in vitro hallmarks of tolerogenicity. Despite these observations, using murine MHC-mismatched skin and heart transplant models, donor-derived drug-modified DCs not only failed to induce tolerance but also accelerated graft rejection. The latter was inhibited by injecting the recipient with anti-CD8 Ab, which removed both CD8(+) T cells and CD8(+) DCs. The discrepancy between in vitro and in vivo data could be explained, partly, by the presentation of drug-modified donor DC MHC alloantigens by recipient APCs and activation of recipient T cells with indirect allospecificity, leading to the induction of alloantibodies. Furthermore, allogeneic MHC molecules expressed by drug-treated DCs were rapidly processed and presented in peptide form by recipient APCs in vivo within hours of DC injection. Using TCR-transgenic T cells, Ag presentation of injected OVA-pulsed DCs was detectable for

Original language	English
Pages (from-to)	4848-4860
Number of pages	13
Journal	Journal of Immunology
Volume	190
Issue number	9
DOIs	https://doi.org/10.4049/jimmunol.1200870
Publication status	Published - 1 May 2013

Keywords

REGULATORY T-CELLS
CARDIAC ALLOGRAFT SURVIVAL
MAJOR HISTOCOMPATIBILITY COMPLEX
COLONY-STIMULATING FACTOR
ANTIGEN-PRESENTING CELLS
MINOR H-ANTIGENS
1-ALPHA,25-DIHYDROXYVITAMIN D-3
TRANSPLANT TOLERANCE
CROSS-PRESENTATION
INDUCE HYPORESPONSIVENESS

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.4049/jimmunol.1200870

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title = "Tolerogenic Donor-Derived Dendritic Cells Risk Sensitization In Vivo owing to Processing and Presentation by Recipient APCs",

abstract = "Modification of allogeneic dendritic cells (DCs) through drug treatment results in DCs with in vitro hallmarks of tolerogenicity. Despite these observations, using murine MHC-mismatched skin and heart transplant models, donor-derived drug-modified DCs not only failed to induce tolerance but also accelerated graft rejection. The latter was inhibited by injecting the recipient with anti-CD8 Ab, which removed both CD8(+) T cells and CD8(+) DCs. The discrepancy between in vitro and in vivo data could be explained, partly, by the presentation of drug-modified donor DC MHC alloantigens by recipient APCs and activation of recipient T cells with indirect allospecificity, leading to the induction of alloantibodies. Furthermore, allogeneic MHC molecules expressed by drug-treated DCs were rapidly processed and presented in peptide form by recipient APCs in vivo within hours of DC injection. Using TCR-transgenic T cells, Ag presentation of injected OVA-pulsed DCs was detectable for ",

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author = "Smyth, {Lesley A.} and Kulachelvy Ratnasothy and Aurelie Moreau and Sally Alcock and Pervinder Sagoo and Lucy Meader and Yakup Tanriver and Matthew Buckland and Robert Lechler and Giovanna Lombardi",

year = "2013",

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doi = "10.4049/jimmunol.1200870",

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AU - Smyth, Lesley A.

AU - Ratnasothy, Kulachelvy

AU - Moreau, Aurelie

AU - Alcock, Sally

AU - Sagoo, Pervinder

AU - Meader, Lucy

AU - Tanriver, Yakup

AU - Buckland, Matthew

AU - Lechler, Robert

AU - Lombardi, Giovanna

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N2 - Modification of allogeneic dendritic cells (DCs) through drug treatment results in DCs with in vitro hallmarks of tolerogenicity. Despite these observations, using murine MHC-mismatched skin and heart transplant models, donor-derived drug-modified DCs not only failed to induce tolerance but also accelerated graft rejection. The latter was inhibited by injecting the recipient with anti-CD8 Ab, which removed both CD8(+) T cells and CD8(+) DCs. The discrepancy between in vitro and in vivo data could be explained, partly, by the presentation of drug-modified donor DC MHC alloantigens by recipient APCs and activation of recipient T cells with indirect allospecificity, leading to the induction of alloantibodies. Furthermore, allogeneic MHC molecules expressed by drug-treated DCs were rapidly processed and presented in peptide form by recipient APCs in vivo within hours of DC injection. Using TCR-transgenic T cells, Ag presentation of injected OVA-pulsed DCs was detectable for

AB - Modification of allogeneic dendritic cells (DCs) through drug treatment results in DCs with in vitro hallmarks of tolerogenicity. Despite these observations, using murine MHC-mismatched skin and heart transplant models, donor-derived drug-modified DCs not only failed to induce tolerance but also accelerated graft rejection. The latter was inhibited by injecting the recipient with anti-CD8 Ab, which removed both CD8(+) T cells and CD8(+) DCs. The discrepancy between in vitro and in vivo data could be explained, partly, by the presentation of drug-modified donor DC MHC alloantigens by recipient APCs and activation of recipient T cells with indirect allospecificity, leading to the induction of alloantibodies. Furthermore, allogeneic MHC molecules expressed by drug-treated DCs were rapidly processed and presented in peptide form by recipient APCs in vivo within hours of DC injection. Using TCR-transgenic T cells, Ag presentation of injected OVA-pulsed DCs was detectable for

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KW - MAJOR HISTOCOMPATIBILITY COMPLEX

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KW - ANTIGEN-PRESENTING CELLS

KW - MINOR H-ANTIGENS

KW - 1-ALPHA,25-DIHYDROXYVITAMIN D-3

KW - TRANSPLANT TOLERANCE

KW - CROSS-PRESENTATION

KW - INDUCE HYPORESPONSIVENESS

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DO - 10.4049/jimmunol.1200870

M3 - Article

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VL - 190

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JO - Journal of Immunology

JF - Journal of Immunology

IS - 9

ER -

Tolerogenic Donor-Derived Dendritic Cells Risk Sensitization In Vivo owing to Processing and Presentation by Recipient APCs

Abstract

Keywords

UN SDGs

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