Administration of CD4+CD25highCD127- regulatory T cells preserves β-cell function in type 1 diabetes in children.

Administration of CD4+CD25highCD127- regulatory T cells preserves β-cell function in type 1 diabetes in children.
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DOI:
10.2337/dc12-0038
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发表时间:
2012-09
期刊:
影响因子:
16.2
通讯作者:
Trzonkowski P
Trzonkowski P
中科院分区:
医学1区
文献类型:
--
作者:
Marek-Trzonkowska N;Mysliwiec M;Dobyszuk A;Grabowska M;Techmanska I;Juscinska J;Wujtewicz MA;Witkowski P;Mlynarski W;Balcerska A;Mysliwska J;Trzonkowski P

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1型糖尿病是一种胰岛被自身反应性T细胞破坏的情况。调节性T细胞(Tregs)的数量和抑制活性的缺陷促进了这一过程。在这里,我们第一次展示了输注自体Tregs可以延长新近诊断的儿童1型糖尿病的缓解时间。我们在确诊后2个月内对10名1型糖尿病儿童(年龄8-16岁)进行了Tregs治疗。4例患者接受10×106Tregs/kg体重,其余6例患者接受20×106Tregs/kg体重。制剂由分类的自体CD_3+CD_4+CD_(25)HighCD127−T细胞组成,在良好的生产实践条件下扩增。未发现该疗法的毒副作用。从输液之日起,外周血中Tregs的百分比显著增加。对这些患者和没有接受Tregs治疗的匹配的1型糖尿病患者进行了随访。在1型糖尿病发病半年后(Tregs输注后4~5个月),8例Tregs治疗的患者仍需每日0.5uI/kg体重的胰岛素,其中2例患者完全脱离胰岛素,而未治疗组缓解结束。此外,治疗组的血浆C-肽水平显著高于未治疗组。这项研究表明,在新近发病的1型糖尿病儿童中,使用Tregs是安全和可耐受的。
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 × 106 Tregs/kg body wt, and the remaining 6 patients received 20 × 106 Tregs/kg body wt. The preparation consisted of sorted autologous CD3+CD4+CD25highCD127− 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.
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