Division of Pediatric Endocrinology, University of California San Francisco, USA; Diabetes Center, University of California San Francisco, San Francisco, CA, USA.
Diabetes Center, University of California San Francisco, San Francisco, CA, USA.
J Autoimmun. 2016 Jul;71:78-87. doi: 10.1016/j.jaut.2016.03.011. Epub 2016 Apr 28.
Type 1 diabetes mellitus (T1DM) results from autoimmune destruction of insulin producing beta cells. Regulatory T cells (Tregs) have been shown to be defective in this setting. Immuno-therapies targeting T cells, and resetting the balance between T effectors and Tregs, have had some initial success in preserving beta cell function. With a goal to use Tregs themselves as a novel therapeutic, we developed a technique to isolate and expand Tregs from patients with T1DM. These ex vivo expanded CD4(+)CD127(lo/-)CD25(+) cells exhibit improved function and retain their T cell receptor diversity. These cells have subsequently been used in phase I clinical trials in patients with recent onset T1DM. The infusions were well tolerated, with no safety concerns. The studies are too small to assess efficacy definitively, although some individuals exhibit stable beta cell function over intervals as long as 2 years. These efforts set the stage for a larger phase II effort in new onset T1DM, and combination studies with other drugs, as well as efforts in other autoimmune diseases.
1 型糖尿病（T1DM）是由于产生胰岛素的β细胞发生自身免疫性破坏所致。在这种情况下，调节性 T 细胞（Tregs）已被证明存在缺陷。针对 T 细胞的免疫疗法，以及重置 T 效应细胞和 Tregs 之间的平衡，在维持β细胞功能方面取得了一些初步成功。为了利用 Tregs 本身作为一种新的治疗方法，我们开发了一种从 T1DM 患者中分离和扩增 Tregs 的技术。这些体外扩增的 CD4(+)CD127(lo/-)CD25(+)细胞表现出改善的功能，并保留其 T 细胞受体多样性。随后，这些细胞已在近期诊断为 T1DM 的患者的 I 期临床试验中使用。输注耐受良好，无安全问题。这些研究的规模太小，无法明确评估疗效，尽管一些患者的β细胞功能在长达 2 年的时间内保持稳定。这些努力为新诊断的 T1DM 进行更大规模的 II 期研究以及与其他药物的联合研究以及其他自身免疫性疾病的研究奠定了基础。
