Jason M. Zimmerer, Hatem Aldhahi, Ginny L. Bumgardner
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引用次数: 0
Abstract
Transplantation is the definitive treatment for patients with end-stage organ failure. Following allogeneic transplant, the recipient's immune system recognizes transplanted cells or organs as foreign. The immune system recognizes and targets the foreign tissue for damage through cell-mediated rejection (CMR) and/or antibody-mediated rejection (AMR). Immunosuppressive agents are utilized to protect the transplant from rejection and extend transplant function and survival. Despite advances in immunosuppressive agents, AMR remains a critical barrier to the success of transplantation. AMR occurs when B cells produce alloantibodies that bind the allograft causing antibody-dependent, complement-mediated or immune cell-mediated cytotoxic damage. Continued research on AMR is required to develop novel and effective therapeutic strategies. Murine AMR models have been utilized to investigate mechanisms mediating the production of posttransplant alloantibodies and the pathology of damage to the transplanted allograft. These models facilitating the investigation of cellular and molecular mechanisms of alloantibody production and allograft damage are critical to the development of novel therapeutic strategies to prevent and treat AMR. This article describes the methodologies used to study AMR in animal transplant models. These include protocols to detect and measure alloantibodies, allograft survival, AMR pathology, and effector immune cell responses following transplantation. © 2025 The Author(s). Current Protocols published by Wiley Periodicals LLC.
Basic Protocol 1: Alloserum transfer into immune-incompetent recipient mice to determine transplant organ susceptibility to AMR
Basic Protocol 2: Allogeneic transplantation into immune-deficient mice to study critical cellular and molecular pathways impacting AMR
Support Protocol 1: Quantification of posttransplant alloantibody titer
Support Protocol 2: Monitoring of transplant allograft survival
Support Protocol 3: Assessment of immunopathology and severity of AMR
Basic Protocol 3: Analysis of posttransplant immunologic responses
研究同种异体抗体介导的移植排斥反应的小鼠模型和实验方案。
移植是终末期器官衰竭患者的最终治疗方法。同种异体移植后,受者的免疫系统将移植的细胞或器官识别为外来的。免疫系统通过细胞介导的排斥反应(CMR)和/或抗体介导的排斥反应(AMR)识别并针对外来组织进行损伤。免疫抑制剂用于保护移植器官免受排斥,延长移植功能和生存。尽管免疫抑制剂取得了进展,但AMR仍然是移植成功的关键障碍。当B细胞产生同种异体抗体结合同种异体移植物引起抗体依赖性、补体介导或免疫细胞介导的细胞毒性损伤时,就会发生AMR。需要继续对抗菌素耐药性进行研究,以开发新的有效的治疗策略。小鼠AMR模型已被用于研究介导移植后同种异体抗体产生的机制和移植同种异体移植物损伤的病理。这些模型有助于研究同种异体抗体产生和同种异体移植物损伤的细胞和分子机制,对于开发预防和治疗AMR的新治疗策略至关重要。本文描述了用于研究动物移植模型中抗菌素耐药性的方法。这些包括检测和测量同种异体抗体、同种异体移植物存活、抗菌素耐药性病理和移植后效应免疫细胞反应的方案。©2025作者。Wiley期刊有限责任公司发表的当前方案:基本方案1:同种异体血清转移到免疫功能不全的受体小鼠中,以确定移植器官对AMR的易感性。基本方案2:同种异体移植到免疫缺陷小鼠中,研究影响AMR的关键细胞和分子途径。支持方案1:移植后同种异体抗体滴度的定量。支持方案2:移植同种异体移植物存活的监测。AMR的免疫病理和严重程度评估基本方案3:移植后免疫反应分析。
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