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Tolerogenic dendritic cells and negative vaccination in transplantation: from rodents to clinical trials

The use of immunosuppressive (IS) drugs to treat transplant recipients has markedly reduced the incidence of acute rejection and early graft loss. However, such treatments have numerous adverse side effects and fail to prevent chronic allograft dysfunction. In this context, therapies based on the ad...

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Autores principales: Moreau, Aurélie, Varey, Emilie, Bériou, Gaëlle, Hill, Marcelo, Bouchet-Delbos, Laurence, Segovia, Mercedes, Cuturi, Maria-Cristina
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3414843/
https://www.ncbi.nlm.nih.gov/pubmed/22908013
http://dx.doi.org/10.3389/fimmu.2012.00218
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author Moreau, Aurélie
Varey, Emilie
Bériou, Gaëlle
Hill, Marcelo
Bouchet-Delbos, Laurence
Segovia, Mercedes
Cuturi, Maria-Cristina
author_facet Moreau, Aurélie
Varey, Emilie
Bériou, Gaëlle
Hill, Marcelo
Bouchet-Delbos, Laurence
Segovia, Mercedes
Cuturi, Maria-Cristina
author_sort Moreau, Aurélie
collection PubMed
description The use of immunosuppressive (IS) drugs to treat transplant recipients has markedly reduced the incidence of acute rejection and early graft loss. However, such treatments have numerous adverse side effects and fail to prevent chronic allograft dysfunction. In this context, therapies based on the adoptive transfer of regulatory cells are promising strategies to induce indefinite transplant survival. The use of tolerogenic dendritic cells (DC) has shown great potential, as preliminary experiments in rodents have demonstrated that administration of tolerogenic DC prolongs graft survival. Recipient DC, Donor DC, or Donor Ag-pulsed recipient DC have been used in preclinical studies and administration of these cells with suboptimal immunosuppression increases their tolerogenic potential. We have demonstrated that autologous unpulsed tolerogenic DC injected in the presence of suboptimal immunosuppression are able to induce Ag-specific allograft tolerance. We derived similar tolerogenic DC in different animal models (mice and non-human primates) and confirmed their protective abilities in vitro and in vivo. The mechanisms involved in the tolerance induced by autologous tolerogenic DC were also investigated. With the aim of using autologous DC in kidney transplant patients, we have developed and characterized tolerogenic monocyte-derived DC in humans. In this review, we will discuss the preclinical studies and describe our recent results from the generation and characterization of tolerogenic monocyte-derived DC in humans for a clinical application. We will also discuss the limits and difficulties in translating preclinical experiments to theclinic.
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spelling pubmed-34148432012-08-20 Tolerogenic dendritic cells and negative vaccination in transplantation: from rodents to clinical trials Moreau, Aurélie Varey, Emilie Bériou, Gaëlle Hill, Marcelo Bouchet-Delbos, Laurence Segovia, Mercedes Cuturi, Maria-Cristina Front Immunol Immunology The use of immunosuppressive (IS) drugs to treat transplant recipients has markedly reduced the incidence of acute rejection and early graft loss. However, such treatments have numerous adverse side effects and fail to prevent chronic allograft dysfunction. In this context, therapies based on the adoptive transfer of regulatory cells are promising strategies to induce indefinite transplant survival. The use of tolerogenic dendritic cells (DC) has shown great potential, as preliminary experiments in rodents have demonstrated that administration of tolerogenic DC prolongs graft survival. Recipient DC, Donor DC, or Donor Ag-pulsed recipient DC have been used in preclinical studies and administration of these cells with suboptimal immunosuppression increases their tolerogenic potential. We have demonstrated that autologous unpulsed tolerogenic DC injected in the presence of suboptimal immunosuppression are able to induce Ag-specific allograft tolerance. We derived similar tolerogenic DC in different animal models (mice and non-human primates) and confirmed their protective abilities in vitro and in vivo. The mechanisms involved in the tolerance induced by autologous tolerogenic DC were also investigated. With the aim of using autologous DC in kidney transplant patients, we have developed and characterized tolerogenic monocyte-derived DC in humans. In this review, we will discuss the preclinical studies and describe our recent results from the generation and characterization of tolerogenic monocyte-derived DC in humans for a clinical application. We will also discuss the limits and difficulties in translating preclinical experiments to theclinic. Frontiers Media S.A. 2012-08-09 /pmc/articles/PMC3414843/ /pubmed/22908013 http://dx.doi.org/10.3389/fimmu.2012.00218 Text en Copyright © 2012 Moreau, Varey, Bériou, Hill, Bouchet-Delbos, Segovia and Cuturi. http://www.frontiersin.org/licenseagreement This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in other forums, provided the original authors and source are credited and subject to any copyright notices concerning any third-party graphics etc.
spellingShingle Immunology
Moreau, Aurélie
Varey, Emilie
Bériou, Gaëlle
Hill, Marcelo
Bouchet-Delbos, Laurence
Segovia, Mercedes
Cuturi, Maria-Cristina
Tolerogenic dendritic cells and negative vaccination in transplantation: from rodents to clinical trials
title Tolerogenic dendritic cells and negative vaccination in transplantation: from rodents to clinical trials
title_full Tolerogenic dendritic cells and negative vaccination in transplantation: from rodents to clinical trials
title_fullStr Tolerogenic dendritic cells and negative vaccination in transplantation: from rodents to clinical trials
title_full_unstemmed Tolerogenic dendritic cells and negative vaccination in transplantation: from rodents to clinical trials
title_short Tolerogenic dendritic cells and negative vaccination in transplantation: from rodents to clinical trials
title_sort tolerogenic dendritic cells and negative vaccination in transplantation: from rodents to clinical trials
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3414843/
https://www.ncbi.nlm.nih.gov/pubmed/22908013
http://dx.doi.org/10.3389/fimmu.2012.00218
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