Trivedi H L
Institute of Kidney Diseases and Transplantation Sciences, Gulabben Rasiklal Doshi and Kamlaben Mafatlal Mehta Institute, Research Center and Institute of Civil Hospital Campus, Asarwa Ahmedabad, Gujarat, India.
Transplant Proc. 2007 Apr;39(3):647-52. doi: 10.1016/j.transproceed.2007.01.047.
Transplantation is an acceptable therapy for failing organs, however, the balance between prevention of acute rejection and immunosuppressant-induced toxicity remains elusive. Organ transplantation from a genetically disparate donor induces an immune response toward donor antigens in the recipient. An uncontrolled cumulative effect of these responses may jeopardize the recipient's life and destroy the grafted tissue. The donor antigen in the form of passenger leukocytes from the allograft migrating to the organized lymphoid collection is a prerequisite for initiation of acute rejection. In the host lymphoid tissue donor-specific dendritic cells primed with donor peptide activate naïve CD4 helper T cells which in turn activate effector CD8 T-cell clones through the release of cytokines. Activated effector CD8 cells return to the graft and augment destructive activity with the help of adhesive molecules and perforin. This seems to be the mechanism of adaptive immunity to destroy viral pathogens; the pattern of allograft injury is not much different. Adaptation and tolerance are based on the principle of exhaustion of donor-specific immune responses by an activation-deletion-exhaustion pathway.
移植是治疗功能衰竭器官的一种可接受的疗法，然而，预防急性排斥反应和免疫抑制剂诱导的毒性之间的平衡仍然难以捉摸。来自基因不同供体的器官移植会在受体中引发针对供体抗原的免疫反应。这些反应的不受控制的累积效应可能危及受体的生命并破坏移植组织。来自移植物的过客白细胞形式的供体抗原迁移到有组织的淋巴集合是引发急性排斥反应的先决条件。在宿主淋巴组织中，用供体肽致敏的供体特异性树突状细胞激活幼稚的CD4辅助性T细胞，后者继而通过细胞因子的释放激活效应性CD8 T细胞克隆。活化的效应性CD8细胞返回移植物，并在黏附分子和穿孔素的帮助下增强破坏活性。这似乎是适应性免疫破坏病毒病原体的机制；同种异体移植物损伤的模式并无太大不同。适应和耐受基于通过激活-缺失-耗竭途径使供体特异性免疫反应耗竭的原理。
