Vlad G, Ho E K, Vasilescu E R, Fan J, Liu Z, Cai J W, Jin Z, Burke E, Deng M, Cadeiras M, Cortesini R, Itescu S, Marboe C, Mancini D, Suciu-Foca N
The Department of Pathology, Columbia University, New York, NY 10032, United States.
Transpl Immunol. 2007 Jul;18(1):13-21. doi: 10.1016/j.trim.2007.03.001. Epub 2007 Apr 2.
The interleukin-2 receptor alpha chain (IL-2Ra, CD25) plays a major part in shaping the dynamics of T cell populations following immune activation, due to its role in T cell proliferation and survival. Strategies to blunt the effector responses in transplantation have been developed by devising pharmaceutical agents to block the IL-2 pathways. However, such strategies could adversely affect the CD25(+)FOXP3(+)T regulatory (T reg) populations which also rely on intereukin-2 signaling for survival. The present study shows that a cohort of heart allograft recipients treated with Daclizumab (a humanized anti-CD25 antibody) display FOXP3 expression patterns consistent with functional T regulatory cell populations. High levels of FOXP3 were observed to correlate with lower incidence of and recovery from acute rejection, as well as lower levels of anti-donor HLA antibody production. Therefore, T reg populations appear fully functional in patients treated with Daclizumab, even when 5 doses were administered. By comparison, patients treated with fewer doses or no Daclizumab had a higher incidence of acute rejection, antibody production and graft failure. Therefore, our data indicates that Daclizumab treatment does not interfere with the generation of regulatory T cells and has a beneficial effect on heart allograft survival.
白细胞介素-2受体α链（IL-2Ra，CD25）在免疫激活后T细胞群体动态形成过程中发挥着重要作用，这归因于其在T细胞增殖和存活方面的作用。通过设计药物阻断IL-2通路，已开发出在移植中减弱效应反应的策略。然而，这些策略可能会对CD25(+)FOXP3(+)调节性T（Treg）细胞群体产生不利影响，该群体的存活同样依赖白细胞介素-2信号传导。本研究表明，一组接受达利珠单抗（一种人源化抗CD25抗体）治疗的心脏移植受者表现出与功能性调节性T细胞群体一致的FOXP3表达模式。观察到高水平的FOXP3与急性排斥反应的发生率降低及从中恢复相关，也与抗供体HLA抗体产生水平降低相关。因此，即使给予5剂达利珠单抗治疗，Treg细胞群体在患者中似乎仍具有完全功能。相比之下，接受较少剂量或未接受达利珠单抗治疗的患者急性排斥反应发生率、抗体产生及移植物失败率更高。因此，我们的数据表明达利珠单抗治疗不会干扰调节性T细胞的产生，并且对心脏移植存活具有有益作用。
