The role of B cells in solid organ transplantation.
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The role of antibodies in chronic injury to organ transplants has been suggested for many years, but recently emphasized by new data. We have observed that when immunosuppressive potency decreases either by intentional weaning of maintenance agents or due to homeostatic repopulation after immune cell depletion, the threshold of B cell activation may be lowered. In human transplant recipients the result may be donor-specific antibody, C4d+ injury, and chronic rejection. This scenario has precise parallels in a rhesus monkey renal allograft model in which T cells are depleted with CD3 immunotoxin, or in a CD52-T cell transgenic mouse model using alemtuzumab to deplete T cells. Such animal models may be useful for the testing of therapeutic strategies to prevent DSA. We agree with others who suggest that weaning of immunosuppression may place transplant recipients at risk of chronic antibody-mediated rejection, and that strategies to prevent this scenario are needed if we are to improve long-term graft and patient outcomes in transplantation. We believe that animal models will play a crucial role in defining the pathophysiology of antibody-mediated rejection and in developing effective therapies to prevent graft injury. Two such animal models are described herein.
Disease Models, Animal
Published Version (Please cite this version)10.1016/j.smim.2011.08.022
Publication InfoBulut, P; Dar, W; Iwakoshi, Neal N; Kim, E; Knechtle, Stuart J; Kwun, J; ... Ruhil, R (2012). The role of B cells in solid organ transplantation. Semin Immunol, 24(2). pp. 96-108. 10.1016/j.smim.2011.08.022. Retrieved from https://hdl.handle.net/10161/10059.
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William R. Kenan, Jr. Professor
During my career as an academic surgeon, I have had the privilege of leading and/or participating in a diverse portfolio of hypothesis-driven research projects. These projects have centered on the immunology of surgery and transplantation, including both cellular and antibody-mediated immune responses. During my training I studied the response of hyper-sensitized recipients to allogeneic liver transplantation, and am currently studying means of reducing immunologic memory that might
Assistant Professor of Surgery
Research interests include humoral tolerance to organ transplants in animal model and humans, developing a clinically relevant animal model to study the mechanisms of antibody-mediated rejection (AMR), and establishing a conceptual basis that will translate into therapeutic intervention of AMR.
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