ISSN:1087-2418    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

Incremental progress in understanding the molecular basis of chronic rejection has occurred, with particular insights arising from the identification of the involvement of indirect allorecognition in disease pathogenesis, as well as ongoing costimulation. Additional new data concern growth factors and cytokines involved in the mediation and amplification of intragraft responses, the activation of nuclear factor kappa-B within graft vascular cells during chronic rejection, and an important developing awareness of the contribution of proapoptotic genes to the remodeling and fibrotic processes underlying chronic rejection. Molecular approaches are now being introduced for diagnostic and prognostic purposes, and progress in gene therapy is finally proving useful, at least experimentally.

ISSN:1087-2418    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

The ongoing investigative efforts to understand the causes, evolution, and pathophysiology of chronic allograft rejection have become a major subject of transplantation research. Because of the persistent rate of attrition of many engrafted organs, a sequential definition of the process is desired to produce new prevention strategies. Early inflammatory events secondary to initial non-specific graft injury are increasingly recognized as playing a critical role in the development of later functional and structural changes. Thus, gaining further insight into these early processes may be an important prerequisite for effective manipulation of the overall chronic process. Recent information surrounding such initial events is reviewed in this article. In addition, the effects of ischemia-reperfusion injury and cytomegalovirus infection, both of which are considered particularly important, are described.

ISSN:1087-2418    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

Accumulating experimental and clinical evidence suggests a major impact of reperfusion injury mediated by reactive oxygen species (ROS) on the development of chronic allograft dysfunction. The underlying mechanisms by which this nonspecific injury contributes to the initiation and progression of chronic allograft dysfunction are not fully understood. Three pathways are addressed in this article: 1) a ROS-mediated disturbance of the microcirculation in renal allografts, which may contribute, in addition to the existence of anaerobic metabolism, to delayed graft function as a risk factor for chronic dysfunction; 2) a ROS-mediated acute endothelial injury at the allograft vessel walls, which leads, in analogy to the response-to-injury hypothesis, to alloatherogenesis as a characteristic sign of chronic allograft dysfunction; and 3) a ROS-mediated global injury to the allograft, which represents, in analogy to the danger hypothesis, the primary key event that initiates alloimmune responsiveness via T-cell activation by facilitating costimulatory processes. These clinically manifesting or subclinically occurring immune events, which are initiated by reperfusion injury as the driving force, contribute specifically to development of chronic allograft dysfunction.

ISSN:1087-2418    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

Recent experimental studies have shown that antibodies alone or in conjunction with T-cell immunity can cause chronic rejection. Because currently used immunosuppressive drugs are mostly effective in suppressing T-cell immunity, antibodies may constitute the dominant effector mechanism of chronic rejection. Antibodies against basement membranes, focal adhesion plaques, and proteins secreted by activated cells may maintain chronic inflammation and interfere in the tissue repair process, resulting in excessive fibrosis. This hypothesis accounts for the association between tissue damage or activation and chronic rejection.

ISSN:1087-2418    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

Experimental results indicate that chronic rejection is the end result of tissue remodeling processes initiated by local tissue injury. This remodeling process can occur within the transplanted organ in the absence of alloantigen but is greatly accelerated in the setting of alloantigen-driven cellular and humoral immune responses. In general, clinical studies have confirmed the importance of alloantigen-driven immune responses (ie, acute rejection and alloantibody production) in the development of chronic rejection. More recent clinical studies have identified other significant, alloantigen-independent risk factors for chronic rejection. The best clinical evidence suggesting the importance of these factors is found in heart, kidney, and lung transplants. Identification of clinical risk factors predictive of chronic rejection is the first step toward development of therapeutic strategies to minimize this significant cause of late graft failure.

ISSN:1087-2418    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

Despite improvements in the prevention and treatment of acute rejection, chronic rejection remains the major cause of long-term graft loss. For renal transplantation, no convincing evidence is available that shows any immunosuppressive protocol prevents the development of chronic rejection or that any available agent ameliorates chronic rejection after it is already established; however, this is in part secondary to the relatively short follow-up period available for many of the newer immunosuppressive regimens. For liver transplantation, it appears that tacrolimus may prevent the development of chronic rejection and may salvage some grafts with preexisting chronic rejection. In the case of cardiac transplantation, the addition of an 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor to standard immunosuppression based on cyclosporine A seems to effectively decrease the development of transplant vasculopathy. This article examines the utility and efficacy of current clinical therapies and promising experimental agents.

ISSN:1087-2418    

出版商:OVID    

年代:1999

数据来源: OVID

ISSN:1087-2418    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

Mixed hematopoietic chimerism is an attractive approach for use in clinical organ transplantation, as it leads to lifelong and robust donor-specific tolerance. Despite numerous successful experimental models, however, routine clinical application has so far been precluded, mainly by the toxicity associated with the conditioning necessary to achieve allogeneic hematopoietic stem cell engraftment. Substantial progress has been achieved in allogeneic and xenogeneic models, notably including the development of considerably less toxic conditioning regimens, and insights into the mechanism of tolerance induction through mixed chimerism have been obtained.

ISSN:1087-2418    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

Intrathymic administration of antigen is a versatile strategy for the induction of tolerance to a wide range of allo-, xeno-, and autoantigens. Interest has now turned to developing methods allowing efficient delivery of antigen to the thymus, and to elucidating the mechanisms responsible for tolerance induction using this route of antigen delivery. Novel approaches for introducing antigen into the thymus, including the use of gene transfer and bone marrow chimeras, have been developed. Recent data utilizing T-cell receptor transgenic animals have shed new light on the mechanisms responsible for acquired intrathymic tolerance.

ISSN:1087-2418    

出版商:OVID    

年代:1999

数据来源: OVID