Department of Clinical Immunology and Transplantology, Medical University of Gdansk, Gdansk,Poland.
Diabetes Care. 2012 Sep;35(9):1817-20. doi: 10.2337/dc12-0038. Epub 2012 Jun 20.
Type 1 diabetes is a condition in which pancreatic islets are destroyed by self-reactive T cells. The process is facilitated by deficits in the number and suppressive activity of regulatory T cells (Tregs). Here, we show for the first time that the infusion of autologous Tregs prolongs remission in recently diagnosed type 1 diabetes in children.
We have administered Tregs in 10 type 1 diabetic children (aged 8-16 years) within 2 months since diagnosis. In total, 4 patients received 10 × 10(6) Tregs/kg body wt, and the remaining 6 patients received 20 × 10(6) Tregs/kg body wt. The preparation consisted of sorted autologous CD3(+)CD4(+)CD25(high)CD127(-) Tregs expanded under good manufacturing practice conditions.
No toxicity of the therapy was noted. A significant increase in the percentage of Tregs in the peripheral blood has been observed since the day of infusion. These patients were followed along with matched type 1 diabetic patients not treated with Tregs. Half a year after type 1 diabetes onset (4-5 months after Tregs infusion), 8 patients treated with Tregs still required <0.5 UI/kg body wt of insulin daily, with 2 patients out of insulin completely, whereas the remission was over in the nontreated group. In addition, plasma C-peptide levels were significantly higher in the treated group as compared with those not treated.
This study shows that the administration of Tregs is safe and tolerable in children with recent-onset type 1 diabetes.
1 型糖尿病是一种由于自身反应性 T 细胞破坏胰岛而导致的疾病。该过程是由调节性 T 细胞（Treg）数量和抑制活性的缺陷所促进的。在这里，我们首次表明，输注自体 Treg 可延长近期诊断为 1 型糖尿病的儿童的缓解期。
我们在诊断后 2 个月内对 10 名 1 型糖尿病儿童（年龄 8-16 岁）输注 Treg。共有 4 名患者接受了 10×10(6)Treg/kg 体重，其余 6 名患者接受了 20×10(6)Treg/kg 体重。该制剂由在良好生产规范条件下分选的自体 CD3(+)CD4(+)CD25(high)CD127(-)Treg 组成。
该疗法未观察到毒性。自输注之日起，外周血中 Treg 的百分比显著增加。这些患者与未接受 Treg 治疗的匹配 1 型糖尿病患者一起随访。在 1 型糖尿病发病后半年（输注 Treg 后 4-5 个月），8 名接受 Treg 治疗的患者仍需要 <0.5 UI/kg 体重的胰岛素，其中 2 名患者完全不需要胰岛素，而未治疗组的缓解期已经结束。此外，与未治疗组相比，治疗组的血浆 C 肽水平显著升高。
本研究表明，在近期诊断为 1 型糖尿病的儿童中，Treg 的给药是安全且耐受的。
