The role of B cells in solid organ transplantation.
The role of B cells in solid organ transplantation.
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DOI：
10.1016/j.smim.2011.08.022
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发表时间：
2012-04
影响因子：
7.8
通讯作者：
Knechtle SJ
中科院分区：
文献类型：
--
作者：
Kwun J;Bulut P;Kim E;Dar W;Oh B;Ruhil R;Iwakoshi N;Knechtle SJ
抗体在器官移植慢性损伤中的作用已被提出多年，但最近新数据强调了这一点。我们观察到，当免疫抑制效力因有意停药或由于免疫细胞耗竭后的稳态重新增殖而降低时，B 细胞激活的阈值可能会降低。在人类移植受者中，结果可能是供体特异性抗体、C4d+损伤和慢性排斥反应。这种情况与用 CD3 免疫毒素消除 T 细胞的恒河猴肾同种异体移植模型或使用阿仑单抗消除 T 细胞的 CD52-T 细胞转基因小鼠模型中具有精确的相似之处。此类动物模型可能有助于测试预防 DSA 的治疗策略。我们同意其他人的观点，即停止免疫抑制可能会使移植受者面临慢性抗体介导的排斥反应的风险，如果我们要改善移植物和患者的长期预后，就需要采取策略来预防这种情况。我们相信，动物模型将在定义抗体介导的排斥反应的病理生理学以及开发预防移植物损伤的有效疗法方面发挥至关重要的作用。本文描述了两种这样的动物模型。
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.
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