抗原特异性调节性T细胞诱导肝脏移植术后免疫耐受的研究

Seeking for effective strategy to induce self-tolerance from organ grafts and reduce even withdraw immunosuppressive drugs (IS) is an eternal pursuit in transplantation field. Regulatory T (Treg) cells are expected to be the most possible biological agent for immune regulation. After ten years of basic research, our team had set up the GMP facility and already started the basic research and clinical trial using natural Treg cells to treat CR for living donor liver transplantation patients, some of the patients are already in the drug reducing procedures. Meanwhile, fourteen SCI papers above IF5.0 have been published recent years, which received a high attention and were widely referenced by industry peers. By the advantage resources of the living donor and recipient in living donor liver transplantation, DC cells from donor were co-cultured with nTreg obtained from host blood to generate antigen-specific Treg cells. SPIO labeling and MRI analysis were used to observe the survival time and distribution of Treg in healthy volunteers; moreover, patients after liver transplantation were treated with antigen-specific Treg cells to induce immune tolerance. The project will become a milestone of immunotherapy for clinical organ transplantation and implement the clinical tolerance to donor grafts eventually.

寻求有效诱导移植物自我耐受治疗策略，进而减少或停用免疫抑制剂，一直是移植领域永恒的追求。调节性T细胞（Treg）被认为是最可能符合该治疗策略的生物制剂。课题组经10年大量基础研究，现已建立专用GMP级转化医学平台，在世界范围内首次启动采用扩增的自然调节性T细胞诱导肝脏移植术后免疫耐受的基础和临床研究，目前项目进展顺利，部分受试者已进入临床减药阶段。发表IF5.0以上SCI论文14篇获得同行高度关注和广泛引证。本组具有活体肝移植供受者同时存在的资源优势，运用供者DC细胞体外诱导受者Treg转化为供体抗原特异性Treg：①超顺磁纳米铁颗粒(SPIO)标记与MRI体外示踪，观测调节性T细胞在体内的存活时间，分布等细胞代谢情况；②Treg注射肝移植患者诱导免疫耐受，分析其保护肝移植物免于排斥的机理。该项目的实现将是临床器官移植免疫治疗的里程碑，最终实现器官移植对供体的临床耐受。

寻求有效诱导移植物自我耐受治疗策略，进而减少或停用免疫抑制剂，一直是移植领域永恒的追求。调节性T细胞（Treg）被认为是最可能符合该治疗策略的生物制剂。本课题自开展以来围绕Treg的基础与临床开展一系列的研究，累计发表SCI论文19篇；临床上建立Treg回输治疗的标准化流程，包括抗原特异性调节性T细胞的分选提纯及体外扩增的标准化操作流程；建立调节性T细胞治疗术后患者免疫状态的针对性监控方案等。顺利开展肝移植患者移植免疫耐受诱导临床试验，目前共17例受试者参与试验，全部受试者中，免疫抑制药物临床撤药5例，撤药率29%；药物减量一半以上受试者10例，减药率58%。该项目的实现将是临床器官移植免疫治疗的里程碑，最终实现器官移植对供体的临床耐受。