The Experts below are selected from a list of 2427 Experts worldwide ranked by ideXlab platform
Rebecca H. Buckley - One of the best experts on this subject based on the ideXlab platform.
-
Transplantation Immunology solid organ and bone marrow
The Journal of Allergy and Clinical Immunology, 2010Co-Authors: Javier Chinen, Rebecca H. BuckleyAbstract:Development of the field of organ and tissue Transplantation has accelerated remarkably since the human MHC was discovered in 1967. Matching of donor and recipient for MHC antigens has been shown to have a significant positive effect on graft acceptance. The roles of the different components of the immune system involved in the tolerance or rejection of grafts and in graft-versus-host disease have been clarified. These components include antibodies, antigen-presenting cells, helper and cytotoxic T-cell subsets, immune cell-surface molecules, signaling mechanisms, and cytokines. The development of pharmacologic and biological agents that interfere with the alloimmune response has had a crucial role in the success of organ Transplantation. Combinations of these agents work synergistically, leading to lower doses of immunosuppressive drugs and reduced toxicity. Reports of significant numbers of successful solid-organ Transplantations include those of the kidneys, liver, heart, and lung. The use of bone marrow Transplantation for hematologic diseases, particularly hematologic malignancies and primary immunodeficiencies, has become the treatment of choice in many of these conditions. Other sources of hematopoietic stem cells are also being used, and diverse immunosuppressive drug regimens of reduced intensity are being proposed to circumvent the mortality associated with the toxicity of these drugs. Gene therapy to correct inherited diseases by means of infusion of gene-modified autologous hematopoietic stem cells has shown efficacy in 2 forms of severe combined immunodeficiency, providing an alternative to allogeneic tissue Transplantation.
-
27 Transplantation Immunology organ and bone marrow
The Journal of Allergy and Clinical Immunology, 2003Co-Authors: Rebecca H. BuckleyAbstract:Abstract The discovery of the human MHC in 1967 launched the field of organ and tissue Transplantation. More than 800,000 such transplants have been performed during this time. Although matching of donor and recipient for MHC antigens was shown to be of great importance and continues to be so, the development of pharmacologic agents and antilymphocyte antibodies that interfere with the process of graft rejection has had a crucial role in the success of organ Transplantation during the past 2 decades. Enormous progress has been made in understanding the immunologic mechanisms of graft rejection and of graft-versus-host disease. The roles of antibodies, antigen-presenting cells, helper and cytotoxic T cells, immune cell surface molecules, and signaling mechanisms and the cytokines they release have been clarified. This understanding is leading to the development of newer immunosuppressive agents targeting various components of the rejection process. Combinations of these agents work synergistically, leading to lower doses and reduced toxicity. Similarly, the development of effective T-cell depletion techniques has been of great importance for bone marrow Transplantation when an HLA-identical sibling is not available. The major obstacle to the performance of solid organ Transplantation currently is the shortage of donor organs. (J Allergy Clin Immunol 2003;111:S733-44.)
-
Transplantation Immunology: Organ and bone marrow
The Journal of Allergy and Clinical Immunology, 2003Co-Authors: Rebecca H. BuckleyAbstract:The discovery of the human MHC in 1967 launched the field of organ and tissue Transplantation. More than 800,000 such transplants have been performed during this time. Although matching of donor and recipient for MHC antigens was shown to be of great importance and continues to be so, the development of pharmacologic agents and antilymphocyte antibodies that interfere with the process of graft rejection has had a crucial role in the success of organ Transplantation during the past 2 decades. Enormous progress has been made in understanding the immunologic mechanisms of graft rejection and of graft-versus-host disease. The roles of antibodies, antigen-presenting cells, helper and cytotoxic T cells, immune cell surface molecules, and signaling mechanisms and the cytokines they release have been clarified. This understanding is leading to the development of newer immunosuppressive agents targeting various components of the rejection process. Combinations of these agents work synergistically, leading to lower doses and reduced toxicity. Similarly, the development of effective T-cell depletion techniques has been of great importance for bone marrow Transplantation when an HLA-identical sibling is not available. The major obstacle to the performance of solid organ Transplantation currently is the shortage of donor organs.
Thomas E. Starzl - One of the best experts on this subject based on the ideXlab platform.
-
the unfinished legacy of liver Transplantation emphasis on Immunology
Hepatology, 2006Co-Authors: Thomas E. Starzl, Fadi G LakkisAbstract:Liver Transplantation radically changed the philosophy of hepatology practice, enriched multiple areas of basic science, and had pervasive ripple effects in law, public policy, ethics, and theology. Why organ engraftment was feasible remained enigmatic, however, until the discovery in 1992 of donor leukocyte microchimerism in long-surviving liver, and other kinds of organ recipients. Following this discovery, the leukocyte chimerism-associated mechanisms were elucidated that directly linked organ and bone marrow Transplantation and eventually clarified the relationship of Transplantation Immunology to the Immunology of infections, neoplasms, and autoimmune disorders. We describe here how the initially controversial paradigm shift mandated revisions of cherished dogmas. With the fresh insight, the reasons for numerous inexplicable phenomena of Transplantation either became obvious or have become susceptible to discriminate experimental testing. The therapeutic implications of the "new Immunology" in hepatology and in other medical disciplines, have only begun to be explored. Apart from Immunology, physiologic investigations of liver Transplantation have resulted in the discovery of growth factors (beginning with insulin) that are involved in the regulation of liver size, ultrastructure, function, and the capacity for regeneration. Such studies have partially explained functional and hormonal relationships of different abdominal organs, and ultimately they led to the cure or palliation by liver Transplantation of more than 2 dozen hepatic-based inborn errors of metabolism. Liver Transplantation should not be viewed as a purely technologic achievement, but rather as a searchlight whose beams have penetrated the murky mist of the past, and continue to potentially illuminate the future.
-
Transplantation tolerance from a historical perspective
Nature Reviews Immunology, 2001Co-Authors: Thomas E. Starzl, Rolf M. ZinkernagelAbstract:Although Transplantation Immunology as a distinctive field began with the development of experimental models that showed the feasibility of bone marrow Transplantation, organ engraftment was accomplished first in humans, and was thought for many years to occur by drastically different mechanisms. Here, we present our view of the concepts of allograft acceptance and acquired tolerance from a historical perspective, and attempt to amalgamate them into simple and unifying rules that might guide improvements in clinical therapy.
-
The Bidirectional Paradigm of Transplant Immunology
Annals of the New York Academy of Sciences, 1995Co-Authors: Thomas E. Starzl, Noriko Murase, Angus W. Thomson, Anthony J. Demetris, Shiguang Qian, Abdul S. Rao, John J. FungAbstract:Until 1992, the conventional view of Transplantation Immunology was what we have referred to as the one-way paradigm (Fig. 1A and B), a conceptual framework that had been extrapolated from the neonatal tolerance model of Billingham, Brent, and Medawar.1,2 In Medawar’s defenseless recipient experiments, and in the parent to offspring F1, hybrid and recipient cytoablation models (Fig. 1A), it was learned in the 1950s that the risk of lethal graft-versus-host disease (GVHD) after splenocyte or bone marrow Transplantation was directly proportional to the degree of MHC incompatibility. FIGURE 1 Transplantation Immunology as seen with the conventional one-way paradigm (A for bone marrow and B for whole organ Transplantation). The two-way paradigm is shown in C (whole organ) and D (bone marrow Transplantation). As early as 1959, it was known that all the same rules applied when whole organs containing immunologically active cells, such as the intestine, were transplanted. Thus, any kind of hematolymphopoietic Transplantation was conceived to be an essentially one-way cellular transaction, yielding either GVHD, rejection, or tolerance.
-
cell migration and chimerism after whole organ Transplantation the basis of graft acceptance
Hepatology, 1993Co-Authors: Thomas E. Starzl, Noriko Murase, Anthony J. Demetris, Massimo Trucco, Camillo Ricordi, Suzanne T Ildstad, H Ramos, Satoru Todo, Andreas G Tzakis, John J. FungAbstract:Improvements in the prevention or control of rejection of the kidney and liver have been largely interchangeable (1, 2) and then applicable, with very little modification, to thoracic and other organs. However, the mechanism by which anti rejection treatment permits any of these grafts to be “accepted” has been an immunological enigma (3, 4). We have proposed recently that the exchange of migratory leukocytes between the transplant and the recipient with consequent long-term cellular chimerism in both is the basis for acceptance of all whole-organ allografts and xenografts (5). Although such chimerism was demonstrated only a few months ago, the observations have increased our insight into Transplantation Immunology and have encouraged the development of alternative therapeutic strategies (6).
John J. Fung - One of the best experts on this subject based on the ideXlab platform.
-
The Bidirectional Paradigm of Transplant Immunology
Annals of the New York Academy of Sciences, 1995Co-Authors: Thomas E. Starzl, Noriko Murase, Angus W. Thomson, Anthony J. Demetris, Shiguang Qian, Abdul S. Rao, John J. FungAbstract:Until 1992, the conventional view of Transplantation Immunology was what we have referred to as the one-way paradigm (Fig. 1A and B), a conceptual framework that had been extrapolated from the neonatal tolerance model of Billingham, Brent, and Medawar.1,2 In Medawar’s defenseless recipient experiments, and in the parent to offspring F1, hybrid and recipient cytoablation models (Fig. 1A), it was learned in the 1950s that the risk of lethal graft-versus-host disease (GVHD) after splenocyte or bone marrow Transplantation was directly proportional to the degree of MHC incompatibility. FIGURE 1 Transplantation Immunology as seen with the conventional one-way paradigm (A for bone marrow and B for whole organ Transplantation). The two-way paradigm is shown in C (whole organ) and D (bone marrow Transplantation). As early as 1959, it was known that all the same rules applied when whole organs containing immunologically active cells, such as the intestine, were transplanted. Thus, any kind of hematolymphopoietic Transplantation was conceived to be an essentially one-way cellular transaction, yielding either GVHD, rejection, or tolerance.
-
cell migration and chimerism after whole organ Transplantation the basis of graft acceptance
Hepatology, 1993Co-Authors: Thomas E. Starzl, Noriko Murase, Anthony J. Demetris, Massimo Trucco, Camillo Ricordi, Suzanne T Ildstad, H Ramos, Satoru Todo, Andreas G Tzakis, John J. FungAbstract:Improvements in the prevention or control of rejection of the kidney and liver have been largely interchangeable (1, 2) and then applicable, with very little modification, to thoracic and other organs. However, the mechanism by which anti rejection treatment permits any of these grafts to be “accepted” has been an immunological enigma (3, 4). We have proposed recently that the exchange of migratory leukocytes between the transplant and the recipient with consequent long-term cellular chimerism in both is the basis for acceptance of all whole-organ allografts and xenografts (5). Although such chimerism was demonstrated only a few months ago, the observations have increased our insight into Transplantation Immunology and have encouraged the development of alternative therapeutic strategies (6).
Robert I. Lechler - One of the best experts on this subject based on the ideXlab platform.
-
Transplantation tolerance
Pediatric Nephrology, 2014Co-Authors: Emma M. Salisbury, David S. Game, Robert I. LechlerAbstract:Although Transplantation has been a standard medical practice for decades, marked morbidity from the use of immunosuppressive drugs and poor long-term graft survival remain important limitations in the field. Since the first solid organ transplant between the Herrick twins in 1954, Transplantation Immunology has sought to move away from harmful, broad-spectrum immunosuppressive regimens that carry with them the long-term risk of potentially life-threatening opportunistic infections, cardiovascular disease, and malignancy, as well as graft toxicity and loss, towards tolerogenic strategies that promote long-term graft survival. Reports of “transplant tolerance” in kidney and liver allograft recipients whose immunosuppressive drugs were discontinued for medical or non-compliant reasons, together with results from experimental models of Transplantation, provide the proof-of-principle that achieving tolerance in organ Transplantation is fundamentally possible. However, translating the reconstitution of immune tolerance into the clinical setting is a daunting challenge fraught with the complexities of multiple interacting mechanisms overlaid on a background of variation in disease. In this article, we explore the basic science underlying mechanisms of tolerance and review the latest clinical advances in the quest for Transplantation tolerance.
C Clayberger - One of the best experts on this subject based on the ideXlab platform.
-
Transplantation Immunology.
Pediatric clinics of North America, 1994Co-Authors: A M Krensky, C ClaybergerAbstract:A major function of the immune response is the discrimination of self from nonself. It is this response that must be overcome in transplant rejection. Progress in understanding these basic immune mechanisms has helped to improve clinical outcome and lays the foundation for a new generation of therapies.
