摘要:

Despite continued improvement in therapies to prevent acute allograft rejection, transplant-associated arteriosclerosis remains a major long-term limitation to successful solid organ transplantation. Ongoing intimal hyperplasia of arterioles results in progressive vascular stenosis with consequent graft ischemia. The process is driven by successive waves of inflammatory cell infiltrates beginning with cells of acute and chronic innate immunity and culminating in alloantigen-specific T cells. Finally, smooth muscle cells, largely derived from host precursor cells, are also recruited into the vessel intima where they proliferate and produce extracellular matrix. The process of inflammatory cell and smooth muscle cell recruitment depends on the coordinated production of chemokines, produced both by graft endothelial cells as well as by previously recruited host inflammatory cells. This article reviews recent progress in our understanding of these small molecular weight mediators and suggests potential novel therapeutic interventionviablockade of chemokine and chemokine receptor interactions.

ISSN:1087-2418    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

Recent clinical breakthroughs indicate that pancreatic islet allografts can reliably reverse diabetes in insulin-dependent patients. However, there are only a limited number of cadaveric organ donors available for islet isolation. There has been an ongoing effort to develop alternative donor sources. Animal tissues form an attractive donor alternative because they can be generated in large numbers and are amendable to genetic engineering. However, there is much less understanding of cellular and humoral immunity to islet xenografts relative to studies of allograft immunity. Furthermore, there is very little information regarding the capacity for generating tolerance to islet xenografts. This review centers on animal models of islet rejection and tolerance. Much discussion focuses on cellular immunity to xenografts in mouse models because most studies have been performed in such small animal systems. Evidence suggests that there is a formidable antigen-specific cellular response to islet xenografts that involves a major contribution of CD4 T cell-mediated donor antigen recognition.

ISSN:1087-2418    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

Transplantation of porcine tissue into humans induces a vigorous immune response directed predominantly at the carbohydrate epitope galactose-&agr;1,3-galactose (Gal). Gal knockout mice, like humans, do not express the enzyme responsible for synthesis of Gal and consequently produce anti-Gal antibodies in response to environmental antigens or deliberate sensitization. The Gal knockout mouse has been widely used as a surrogate recipient of Gal-expressing grafts. This small animal model has been invaluable in analysis of the immune response to Gal and in the development and testing of various strategies to prevent Gal-mediated xenograft rejection.

ISSN:1087-2418    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

Hyperacute rejection of vascularized discordant xenografts is induced by natural antibodies and mediated by complement and associated coagulation factor activation. This immediate rejection process can now be effectively managed by complement inhibition. However, acute vascular rejection or delayed xenograft rejection then ensues and can result in destruction of the organ within days to weeks. This form of rejection is associated with vascular inflammation, thrombocytopenia, and the consumption of coagulation factors. Primary biologic incompatibilities of the xenograft with respect to regulation of clotting could further amplify this process. Additionally, infection of the xenograft vascular endothelium by cytomegalovirus or other pathogens may cause severe vascular injury. Interventions with standard and novel anticoagulant/antithrombotic therapies in a systemic or targeted manner should have beneficial effects with respect to prolongation of xenograft survival. This article focuses on the progress that has been made toward the understanding of the coagulation disturbances accompanying xenotransplantation.

ISSN:1087-2418    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

Induction of tolerance is likely to be necessary for the achievement of successful xenotransplantation, because immune responses against xenogeneic tissues or organs are vigorous. Currently, protocols that allow prolongation of xenogeneic grafts in preclinical large animal models are not clinically applicable, because the immunosuppressive regimens induce significant morbidity and mortality. This review focuses on the progress that has been made in the strategies that aim to induce donor-specific xenogeneic tolerance, which are largely based on the transplantation of thymic tissue, the induction of molecular chimerism, and the induction of mixed hematopoietic cell chimerism.

ISSN:1087-2418    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

The presence of Gal&agr;1,3Gal epitopes on the vascular endothelium of pigs and of natural anti-Gal antibodies only in humans and Old World nonhuman primates necessitates the use of these nonhuman primates in xenotransplantation models involving pig organs. Recent work has concentrated attention largely on methods of maintaining low natural anti-Gal antibody levels, of preventing the production of elicited antipig antibodies, and/or of inhibiting the activity of complement. The immunologic problems related to pig lung transplantation in nonhuman primates would appear to be accelerated and to have a greater severity than those related to other pig organs. Efforts continue to induce tolerance to pig antigens by mixed hematopoietic chimerism, although this approach has been hindered by the development of a thrombotic microangiopathy directly associated with the presence of pig cells in primate blood.

ISSN:1087-2418    

出版商:OVID    

年代:2003

数据来源: OVID

ISSN:1087-2418    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

Hematopoietic stem cell transplantation aims to restore ablated myelopoiesis caused by intensive chemoradiotherapy. A minimum quantity of progenitor cells must be administered to the patients for adequate engraftment to occur (that is, to cover demanding daily needs of erythrocytes, neutrophils, and platelets). This gives the idea that the higher the quantity of progenitor cells infused to the patients, the better the results after the transplant. However, after reviewing our own data and data from other groups, it appears that the specific clinical effect of the amount of progenitor cells may depend on several factors: (1) the type of transplants, autologous or allogeneic; (2) the source of progenitor cells, either from umbilical cord, from bone marrow, or from peripheral blood; (3) the presence and the quantity of accessory cells, not only T cells, but also dendritic cells (DC1 and DC2) and mesenchymal cells; (4) the degree of human leukocyte antigen (HLA) compatibility; and (5) the underlying disease and the phase of the disease.

ISSN:1087-2418    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

The use of a human leukocyte antigen compatible unrelated donor is a valid option for candidates of allogeneic transplantation without a family member match. The current access to large registries including almost 8 million human leukocyte antigen typed volunteers makes this type of transplants feasible. Grafts from unrelated donors provide long-term disease-free survival for a remarkable proportion of patients with the results depending on patient's age, disease, disease stage, degree of human leukocyte antigen matching with the donor, and progenitor cell dose infused. Prevention and treatment of graft-versus-host disease and opportunistic infections remain a challenge. With more precise donor selection by means of high-resolution DNA techniques, the results of transplants from unrelated donors are approaching to those achieved with human leukocyte antigen identical siblings. The identification of permissible mismatches and the refinement of transplantation techniques will improve the results of this type of transplant in the near future.

ISSN:1087-2418    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

Umbilical cord blood is an appealing alternative source of hematopoietic stem cells for children and adults undergoing transplantation for a wide variety of diseases. Shorter time to transplant, which is particularly relevant for patients requiring urgent transplantation, and tolerance of 1–2 human leukocyte antigen mismatches, which increases the chance of finding a suitable donor, are evident advantages over bone marrow transplantation from unrelated donors. The speed of engraftment is slower after cord blood transplantation, but this is counterbalanced by a lower incidence of severe graft-versus-host disease. Cell dose and human leukocyte antigen are major factors influencing the outcomes of umbilical cord blood transplantation. Unrelated donor cord blood is considered an acceptable alternative to bone marrow for pediatric transplantation, and recent data in adults point the same way. This review describes the current status of cord blood transplantation and discusses developing research strategies aimed at optimizing this kind of transplantation.

ISSN:1087-2418    

出版商:OVID    

年代:2003

数据来源: OVID