Department of Medicine, University of California, San Francisco, CA.
Department of Surgery, University of California, San Francisco, CA.
Am J Transplant. 2017 Nov;17(11):2945-2954. doi: 10.1111/ajt.14415. Epub 2017 Aug 14.
Early subclinical inflammation in kidney transplants is associated with later graft fibrosis and dysfunction. Regulatory T cells (Tregs) can reverse established inflammation in animal models. We conducted a pilot safety and feasibility trial of autologous Treg cell therapy in three kidney transplant recipients with subclinical inflammation noted on 6-month surveillance biopsies. Tregs were purified from peripheral blood and polyclonally expanded ex vivo using medium containing deuterated glucose to label the cells. All patients received a single infusion of ~320 × 10 (319, 321, and 363.8 × 10 ) expanded Tregs. Persistence of the infused Tregs was tracked. Graft inflammation was monitored with follow-up biopsies and urinary biomarkers. Nearly 1 × 10 (0.932, 0.956, 1.565 × 10 ) Tregs were successfully manufactured for each patient. There were no infusion reactions or serious therapy-related adverse events. The infused cells demonstrated patterns of persistence and stability similar to those observed in non-immunosuppressed subjects receiving the same dose of Tregs. Isolation and expansion of Tregs is feasible in kidney transplant patients on immunosuppression. Infusion of these cells was safe and well tolerated. Future trials will test the efficacy of polyclonal and donor alloantigen-reactive Tregs for the treatment of inflammation in kidney transplants.
早期移植肾的亚临床炎症与后期移植物纤维化和功能障碍有关。调节性 T 细胞（Tregs）可以在动物模型中逆转已建立的炎症。我们对 3 名在 6 个月监测活检中出现亚临床炎症的肾移植受者进行了自体 Treg 细胞治疗的安全性和可行性的初步试验。Tregs 从外周血中纯化并在含有氘代葡萄糖的培养基中进行体外多克隆扩增以标记细胞。所有患者均接受了单次约 320×10（319、321 和 363.8×10）个扩增 Treg 的输注。跟踪输注 Treg 的持久性。通过随访活检和尿生物标志物监测移植物炎症。每个患者成功制造了近 1×10（0.932、0.956、1.565×10）个 Treg。没有发生输注反应或严重的治疗相关不良事件。输注的细胞表现出与在接受相同剂量 Treg 的非免疫抑制受试者中观察到的相似的持久性和稳定性模式。在接受免疫抑制治疗的肾移植患者中，Treg 的分离和扩增是可行的。输注这些细胞是安全且耐受良好的。未来的试验将测试多克隆和供体同种抗原反应性 Treg 治疗肾移植炎症的疗效。
