Polyclonal Regulatory T Cell Therapy for Control of Inflammation in Kidney Transplants.
Polyclonal Regulatory T Cell Therapy for Control of Inflammation in Kidney Transplants.
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DOI：
10.1111/ajt.14415
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发表时间：
2017-11
期刊：
影响因子：
--
通讯作者：
Vincenti F
中科院分区：
文献类型：
--
作者：
Chandran S;Tang Q;Sarwal M;Laszik ZG;Putnam AL;Lee K;Leung J;Nguyen V;Sigdel T;Tavares EC;Yang JYC;Hellerstein M;Fitch M;Bluestone JA;Vincenti F
肾移植早期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（Tcells）可以逆转动物模型中已建立的炎症。我们在三名肾移植受者中进行了一项自体Treg细胞治疗的安全性和可行性试验，这些受者在6个月的监测活检中发现了亚临床炎症。从外周血中纯化T细胞，并使用含有氘代葡萄糖的培养基离体多克隆扩增以标记细胞。所有患者均接受了~320 × 106（319、321和363.8 × 106）扩张TdR的单次输注。追踪输注的调节性T细胞的持续性。移植物炎症监测与后续活检和尿生物标志物。为每例患者成功生产了近1 × 109（0.932、0.956、1.565 × 109）个TBI。未发生输注反应或严重治疗相关不良事件。输注的细胞表现出的持久性和稳定性模式与在接受相同剂量TdR的非免疫抑制受试者中观察到的相似。在免疫抑制的肾移植患者中分离和扩增THBG是可行的。输注这些细胞是安全的，耐受性良好。未来的试验将测试多克隆和供体同种异体抗原反应性Tclase治疗肾移植炎症的疗效。
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 × 106 (319, 321 and 363.8 × 106) expanded Tregs. Persistence of the infused Tregs was tracked. Graft inflammation was monitored with follow-up biopsies and urinary biomarkers. Nearly 1 × 109 (0.932, 0.956, 1.565 × 109) 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.
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影响因子：
120.1
作者：
Vincenti, Flavio;Dritselis, Argyris;Kirkpatrick, Peter
通讯作者：
Kirkpatrick, Peter
影响因子：
8.8
作者：
Vincenti, F.;Charpentier, B.;Larsen, C. P.
通讯作者：
Larsen, C. P.
影响因子：
158.5
作者：
Ekberg, Henrik;Tedesco-Silva, Helio;Halloran, Philip F.
通讯作者：
Halloran, Philip F.
DOI：
10.1111/ajt.12928
发表时间：
2014-11
期刊：
American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons
影响因子：
--
作者：
Gandolfini I;Buzio C;Zanelli P;Palmisano A;Cremaschi E;Vaglio A;Piotti G;Melfa L;La Manna G;Feliciangeli G;Cappuccilli M;Scolari MP;Capelli I;Panicali L;Baraldi O;Stefoni S;Buscaroli A;Ridolfi L;D'Errico A;Cappelli G;Bonucchi D;Rubbiani E;Albertazzi A;Mehrotra A;Cravedi P;Maggiore U
通讯作者：
Maggiore U
影响因子：
6.2
作者：
Vanrenterghem, Yves;Bresnahan, Barbara;Vincenti, Flavio
通讯作者：
Vincenti, Flavio