Administration of CD4+CD25highCD127− Regulatory T Cells Preserves β-Cell Function in Type 1 Diabetes in Children

作者：Natalia Maria Marek-Trzonkowska, Małgorzata Myśliwiec, Anita Dobyszuk, Marcelina Grabowska, Ilona Techmańska, Jolanta Juścińska, Magdalena Anna Wujtewicz, Piotr Witkowski, Wojciech Michal Mlynarski, Anna Balcerska, Jolanta M. Myśliwska, Piotr Trzonkowski · 发表于：Diabetes Care · 年份：2012 · DOI：10.2337/dc12-0038 · 被引用次数：435 · 研究领域：Diabetes and associated disorders、Pancreatic function and diabetes、T-cell and B-cell Immunology

OBJECTIVE: 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. RESEARCH DESIGN AND METHODS: 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. RESULTS: 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. CONCLUSIONS: This study shows that the administration of Tregs is safe and tolerable in children wi...