Type 1 diabetes immunotherapy using polyclonal regulatory T cells.
Type 1 diabetes immunotherapy using polyclonal regulatory T cells.
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DOI：
10.1126/scitranslmed.aad4134
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发表时间：
2015-11-25
影响因子：
17.1
通讯作者：
Tang Q
中科院分区：
文献类型：
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作者：
Bluestone JA;Buckner JH;Fitch M;Gitelman SE;Gupta S;Hellerstein MK;Herold KC;Lares A;Lee MR;Li K;Liu W;Long SA;Masiello LM;Nguyen V;Putnam AL;Rieck M;Sayre PH;Tang Q
1型糖尿病（T1D）是一种发生在遗传易感个体的自身免疫性疾病。调节性T细胞（Tregs）已被证明在自身免疫性疾病中存在缺陷。因此，修复或替换T1D中的Tregs可能会逆转自身免疫并保护剩余的产生胰岛素的β细胞。基于这一前提，已经开发出一种强大的技术来分离和扩增T1D患者的treg。扩增后的Tregs保留了其T细胞受体的多样性，并表现出增强的功能活性。我们报告了一项评估Treg过继免疫治疗T1D安全性的1期试验。在四个给药队列中，14名成年T1D患者接受体外扩增的自体CD4+CD127lo/ - CD25+多克隆Tregs （0.05 × 108至26 × 108细胞）。移入的Tregs的一个子集寿命很长，在移入后1年仍有高达25%的峰值水平留在循环中。免疫研究显示受者Treg短暂增加，并长期保持Treg FOXP3+CD4+CD25hiCD127lo表型。没有输液反应或细胞治疗相关的严重不良事件。在一些个体中，c肽水平在转移后持续了2年以上。这些结果支持开展第二阶段试验，以测试Treg疗法的疗效。
Type 1 diabetes (T1D) is an autoimmune disease that occurs in genetically susceptible individuals. Regulatory T cells (Tregs) have been shown to be defective in the autoimmune disease setting. Thus, efforts to repair or replace Tregs in T1D may reverse autoimmunity and protect the remaining insulin-producing β cells. On the basis of this premise, a robust technique has been developed to isolate and expand Tregs from patients with T1D. The expanded Tregs retained their T cell receptor diversity and demonstrated enhanced functional activity. We report on a phase 1 trial to assess safety of Treg adoptive immunotherapy in T1D. Fourteen adult subjects with T1D, in four dosing cohorts, received ex vivo–expanded autologous CD4+CD127lo/−CD25+ polyclonal Tregs (0.05 × 108 to 26 × 108 cells). A subset of the adoptively transferred Tregs was long-lived, with up to 25% of the peak level remaining in the circulation at 1 year after transfer. Immune studies showed transient increases in Tregs in recipients and retained a broad Treg FOXP3+CD4+CD25hiCD127lo phenotype long-term. There were no infusion reactions or cell therapy–related high-grade adverse events. C-peptide levels persisted out to 2+ years after transfer in several individuals. These results support the development of a phase 2 trial to test efficacy of the Treg therapy.