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Hematopoietic Chimerism and Transplantation Tolerance: A Role for Regulatory T Cells
The immunosuppressive regimens currently used in transplantation to prevent allograft destruction by the host’s immune system have deleterious side effects and fail to control chronic rejection processes. Induction of donor-specific non-responsiveness (i.e., immunological tolerance) to transplants w...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Research Foundation
2011
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3342389/ https://www.ncbi.nlm.nih.gov/pubmed/22566869 http://dx.doi.org/10.3389/fimmu.2011.00080 |
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author | Pasquet, Lise Joffre, Olivier Santolaria, Thibault van Meerwijk, Joost P. M. |
author_facet | Pasquet, Lise Joffre, Olivier Santolaria, Thibault van Meerwijk, Joost P. M. |
author_sort | Pasquet, Lise |
collection | PubMed |
description | The immunosuppressive regimens currently used in transplantation to prevent allograft destruction by the host’s immune system have deleterious side effects and fail to control chronic rejection processes. Induction of donor-specific non-responsiveness (i.e., immunological tolerance) to transplants would solve these problems and would substantially ameliorate patients’ quality of life. It has been proposed that bone marrow or hematopoietic stem-cell transplantation, and resulting (mixed) hematopoietic chimerism, lead to immunological tolerance to organs of the same donor. However, a careful analysis of the literature, performed here, clearly establishes that whereas hematopoietic chimerism substantially prolongs allograft survival, it does not systematically prevent chronic rejection. Moreover, the cytotoxic conditioning regimens used to achieve long-term persistence of chimerism are associated with severe side effects that appear incompatible with a routine use in the clinic. Several laboratories recently embarked on different studies to develop alternative strategies to overcome these issues. We discuss here recent advances obtained by combining regulatory T cell infusion with bone-marrow transplantation. In experimental settings, this attractive approach allows development of genuine immunological tolerance to donor tissues using clinically relevant conditioning regimens. |
format | Online Article Text |
id | pubmed-3342389 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2011 |
publisher | Frontiers Research Foundation |
record_format | MEDLINE/PubMed |
spelling | pubmed-33423892012-05-07 Hematopoietic Chimerism and Transplantation Tolerance: A Role for Regulatory T Cells Pasquet, Lise Joffre, Olivier Santolaria, Thibault van Meerwijk, Joost P. M. Front Immunol Immunology The immunosuppressive regimens currently used in transplantation to prevent allograft destruction by the host’s immune system have deleterious side effects and fail to control chronic rejection processes. Induction of donor-specific non-responsiveness (i.e., immunological tolerance) to transplants would solve these problems and would substantially ameliorate patients’ quality of life. It has been proposed that bone marrow or hematopoietic stem-cell transplantation, and resulting (mixed) hematopoietic chimerism, lead to immunological tolerance to organs of the same donor. However, a careful analysis of the literature, performed here, clearly establishes that whereas hematopoietic chimerism substantially prolongs allograft survival, it does not systematically prevent chronic rejection. Moreover, the cytotoxic conditioning regimens used to achieve long-term persistence of chimerism are associated with severe side effects that appear incompatible with a routine use in the clinic. Several laboratories recently embarked on different studies to develop alternative strategies to overcome these issues. We discuss here recent advances obtained by combining regulatory T cell infusion with bone-marrow transplantation. In experimental settings, this attractive approach allows development of genuine immunological tolerance to donor tissues using clinically relevant conditioning regimens. Frontiers Research Foundation 2011-12-28 /pmc/articles/PMC3342389/ /pubmed/22566869 http://dx.doi.org/10.3389/fimmu.2011.00080 Text en Copyright © 2011 Pasquet, Joffre, Santolaria and van Meerwijk. http://www.frontiersin.org/licenseagreement This is an open-access article distributed under the terms of the Creative Commons Attribution Non Commercial License, which permits non-commercial use, distribution, and reproduction in other forums, provided the original authors and source are credited. |
spellingShingle | Immunology Pasquet, Lise Joffre, Olivier Santolaria, Thibault van Meerwijk, Joost P. M. Hematopoietic Chimerism and Transplantation Tolerance: A Role for Regulatory T Cells |
title | Hematopoietic Chimerism and Transplantation Tolerance: A Role for Regulatory T Cells |
title_full | Hematopoietic Chimerism and Transplantation Tolerance: A Role for Regulatory T Cells |
title_fullStr | Hematopoietic Chimerism and Transplantation Tolerance: A Role for Regulatory T Cells |
title_full_unstemmed | Hematopoietic Chimerism and Transplantation Tolerance: A Role for Regulatory T Cells |
title_short | Hematopoietic Chimerism and Transplantation Tolerance: A Role for Regulatory T Cells |
title_sort | hematopoietic chimerism and transplantation tolerance: a role for regulatory t cells |
topic | Immunology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3342389/ https://www.ncbi.nlm.nih.gov/pubmed/22566869 http://dx.doi.org/10.3389/fimmu.2011.00080 |
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