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

Details

Serval ID
serval:BIB_0E26D551F078
Type
Article: article from journal or magazin.
Publication sub-type
Review (review): journal as complete as possible of one specific subject, written based on exhaustive analyses from published work.
Collection
Publications
Institution
Title
Tolerance-inducing immunosuppressive strategies in clinical transplantation: an overview.
Journal
Drugs
Author(s)
Golshayan D., Pascual M.
ISSN
0012-6667[print], 0012-6667[linking]
Publication state
Published
Issued date
2008
Volume
68
Number
15
Pages
2113-2130
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't ; Review
Publication Status: ppublish
Abstract
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.
Keywords
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
Create date
18/02/2009 9:46
Last modification date
20/08/2019 12:35
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