滤泡辅助性T细胞及其在抗体介导的肺移植排斥反应中作用的研究进展

doi:10.3969/j.issn.1006-7795.2023.02.002

摘要/Abstract

摘要：

伴有新生供者特异性抗体(donor-specific antibodies, DSA）产生的体液免疫或抗体介导的排斥反应已成为器官移植后长期生存的重要障碍，1/3同种异体移植物的功能丧失与之密切相关。由于肺区别于其他实体器官，致使约50%接受同种异体肺移植的患者都会发生慢性排斥反应，临床表现为慢性移植肺功能障碍(chronic lung allograft dysfunction, CLAD）。肺移植慢性排斥反应具有两种不同的临床亚型：限制性CLAD(restrictive CLAD, rCLAD）或称限制性移植物综合征(restrictive allograft syndrome, RAS）和闭塞性细支气管炎综合征(bronchiolitis obliterans syndrome, BOS），其中rCLAD/RAS患者的生存率明显低于BOS患者。最新的小鼠模型研究证实，B细胞及其分泌的供者特异性抗体(即同种抗体）在肺移植后RAS的同种移植物纤维化中发挥了不可或缺的作用。因此，为了预防和更好地治疗肺移植患者的同种异体排斥反应，需要深入探究启动和维持B细胞介导的抗供者免疫应答的具体机制。近年来越来越多的研究表明，同种抗体反应在很大程度上依赖于滤泡辅助性T(follicular helper T, Tfh）细胞的作用。本文对Tfh细胞的功能及其在抗体介导的排斥反应(antibody-mediated rejection, AMR）中作用的最新研究进展予以综述，并讨论了可能的干预策略。

关键词: 滤泡辅助性T细胞, 滤泡调节性T细胞, 肺移植, 抗体介导的排斥反应, 供者特异性抗体

Abstract:

Antibody-mediated or humoral rejection in combination with development of de novo donor-specific antibodies (DSA) has been recognized as a significant barrier for long term transplant survival and is responsible for one third of the failed allografts. The lung is one of the most susceptible organs for chronic lung allograft dysfunction (CLAD) which affects about 50% of lung transplant patients. There are two different phenotypes of chronic rejection of lung allografts: (1) restrictive CLAD (rCLAD) or restrictive allograft syndrome (RAS), and (2) bronchiolitis obliterans syndrome (BOS). Patients with rCLAD/RAS have a significantly worse survival compared with BOS patients. Newest studies in mouse model establish an obligatory role for DSA (or alloantibody) production by B cells in the allograft fibrogenesis in RAS after lung transplantation. Therefore, a detailed knowledge of the mechanisms that initiate and maintain B-cell driven anti-donor reactivity is required to prevent and better treat alloresponse in lung transplant patients. During recent years, it became clear that alloantibody response largely depends on the actions of follicular helper T (Tfh) cells. In this overview paper, we review the latest insights on the functions of Tfh cells and their roles in antibody-mediated rejection (AMR), and discuss possible strategies of intervention.

Key words: follicular helper T cells, follicular regulatory T cells, lung transplantation, antibody-mediated rejection, donor-specific antibodies

中图分类号:

R392

王艺, 丁跃中, 许江南. 滤泡辅助性T细胞及其在抗体介导的肺移植排斥反应中作用的研究进展[J]. 首都医科大学学报, 2023, 44(2): 186-195.

Wang Yi, Ding Yuezhong, Xu Jiangnan. Research progress of follicular helper T cells and their roles in antibody-mediated lung transplant rejection[J]. Journal of Capital Medical University, 2023, 44(2): 186-195.

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