Tolerance-inducing immunosuppressive strategies in clinical transplantation: an overview.

Détails

ID Serval
serval:BIB_0E26D551F078
Type
Article: article d'un périodique ou d'un magazine.
Sous-type
Synthèse (review): revue aussi complète que possible des connaissances sur un sujet, rédigée à partir de l'analyse exhaustive des travaux publiés.
Collection
Publications
Titre
Tolerance-inducing immunosuppressive strategies in clinical transplantation: an overview.
Périodique
Drugs
Auteur(s)
Golshayan D., Pascual M.
ISSN
0012-6667[print], 0012-6667[linking]
Statut éditorial
Publié
Date de publication
2008
Volume
68
Numéro
15
Pages
2113-2130
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't ; Review
Publication Status: ppublish
Résumé
The significant development of immunosuppressive drug therapies within the past 20 years has had a major impact on the outcome of clinical solid organ transplantation, mainly by decreasing the incidence of acute rejection episodes and improving short-term patient and graft survival. However, long-term results remain relatively disappointing because of chronic allograft dysfunction and patient morbidity or mortality, which is often related to the adverse effects of immunosuppressive treatment. Thus, the induction of specific immunological tolerance of the recipient towards the allograft remains an important objective in transplantation. In this article, we first briefly describe the mechanisms of allograft rejection and immune tolerance. We then review in detail current tolerogenic strategies that could promote central or peripheral tolerance, highlighting the promises as well as the remaining challenges in clinical transplantation. The induction of haematopoietic mixed chimerism could be an approach to induce robust central tolerance, and we describe recent encouraging reports of end-stage kidney disease patients, without concomitant malignancy, who have undergone combined bone marrow and kidney transplantation. We discuss current studies suggesting that, while promoting peripheral transplantation tolerance in preclinical models, induction protocols based on lymphocyte depletion (polyclonal antithymocyte globulins, alemtuzumab) or co-stimulatory blockade (belatacept) should, at the current stage, be considered more as drug-minimization rather than tolerance-inducing strategies. Thus, a better understanding of the mechanisms that promote peripheral tolerance has led to newer approaches and the investigation of individualized donor-specific cellular therapies based on manipulated recipient regulatory T cells.
Mots-clé
Animals, Graft Rejection/drug therapy, Graft Rejection/prevention &amp, control, Humans, Immunosuppressive Agents/therapeutic use, Leukocytes/drug effects, Leukocytes/immunology, Long-Term Care, Signal Transduction/physiology, T-Lymphocytes/drug effects, T-Lymphocytes/immunology, Transplantation Immunology/drug effects, Transplantation Tolerance/drug effects
Pubmed
Web of science
Création de la notice
18/02/2009 9:46
Dernière modification de la notice
20/08/2019 12:35
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