By Eli A. Friedman, Mary C. Mallappallil
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Extra info for Present and Future Therapies for End-Stage Renal Disease
Qxd 2/1/2010 5:14 PM Page 57 Kidney Transplantation 57 of molecular biology and genomic medicine will probably take us to places we cannot yet imagine. References 1. Osler W. (1901) The Principles and Practice of Medicine, 4th ed. D Appleton, New York. 2. Kolff W, Berk H, Welle M, van der Ley A, van Djik E, van Noordwijk J. (1944) The artificial kidney: a dialyser with a great area. Acta Med Scand 177: 121–134. 3. Silverstein A. (1989) A History of Immunology. Academic, San Diego. 4. Brent L. (1997) A History of Transplantation Immunology.
Similar to immunoglobulins, the T-cell receptor (TCR) is a heterodimer of two polypeptides that have highly variable regions for antigen binding. qxd 2/1/2010 5:14 PM 50 Page 50 Fasika Tedla through additional surface molecules. Presentation of antigen to T-lymphocytes in the absence of the latter, called costimulation, results in anergy instead of activation, and eventual death by apoptosis. 65,66 The dissection of these pathways is a very active area of research at present. Concurrent presence of TCR engagement and positive costimulation recruits several other molecules that trigger intracellular signaling and T-cell activation.
80,81 Compared to patients on the kidney waiting list, transplant recipients develop more oral, skin, renal and lymphoid malignancies, and Kaposi’s sarcoma. Posttransplant lymphoproliferative disorder (PTLD) represents a spectrum of neoplastic processes, ranging from benign polyclonal hyperplasia to aggressive high-grade lymphoma. qxd 2/1/2010 5:14 PM 56 Page 56 Fasika Tedla patients. 82 Although some studies have found association with specific immunosuppressive agents, the risk of PTLD is most likely related to the overall degree of immunosuppression.