Administration of CD4 +CD25 highCD127 - regulatory T cells preserves β-cell function in type 1 diabetes in children

Abstract

OBJECTIVE - Type 1 diabetes is a condition in which pancreatic islets are destroyed by selfreactive 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 highCD127 - 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 withmatched 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 with recent-onset type 1 diabetes. © 2012 by the American Diabetes Association.