Department of Internal Medicine - Nephrology & Transplantation, The Rotterdam Transplant Group, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands.
HLA. 2019 Nov;94(5):407-414. doi: 10.1111/tan.13671. Epub 2019 Sep 8.
Over the past decade, antibody-mediated or humoral rejection in combination with development of de novo donor-specific antibodies (DSA) has been recognized as a distinct and common cause of transplant dysfunction and is responsible for one-third of the failed allografts. Detailed knowledge of the mechanisms that initiate and maintain B-cell driven antidonor reactivity is required to prevent and better treat this antidonor response in organ transplant patients. Over the past few years, it became evident that this response largely depends on the actions of both T follicular helper (Tfh) cells and the controlling counterparts, the T follicular regulatory (Tfr) cells. In this overview paper, we review the latest insights on the functions of circulating (c)Tfh cells, their subsets Tfh1, Tfh2 and Tfh17 cells, IL-21 and Tfr cells in antibody mediated rejection (ABMR). This may offer new insights in the process to reduce de novo DSA secretion resulting in a decline in the incidence of ABMR. In addition, monitoring these cell populations could be helpful for the development of biomarkers identifying patients at risk for ABMR and provide novel therapeutic drug targets to treat ABMR.
在过去的十年中，抗体介导的或体液性排斥反应与新出现的供体特异性抗体（DSA）的发展相结合，已被认为是移植功能障碍的一个独特且常见的原因，占移植失败的三分之一。为了预防和更好地治疗器官移植患者的这种抗供体反应，需要详细了解启动和维持 B 细胞驱动的抗供体反应的机制。在过去的几年中，很明显，这种反应在很大程度上取决于滤泡辅助性 T 细胞（Tfh）和控制细胞滤泡调节性 T 细胞（Tfr）的作用。在这篇综述中，我们回顾了关于循环（c）Tfh 细胞、其亚群 Tfh1、Tfh2 和 Tfh17 细胞、IL-21 和 Tfr 细胞在抗体介导的排斥反应（ABMR）中的最新功能的见解。这可能为减少新出现的 DSA 分泌从而降低 ABMR 的发生率提供新的见解。此外，监测这些细胞群可能有助于开发识别 ABMR 风险患者的生物标志物，并为治疗 ABMR 提供新的治疗药物靶点。
