Administration of CD4+CD25highCD127- 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 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 with recent-onset type 1 diabetes.

Figure 1

C-peptide, DDI, HbA_1c, and fasting glucose in type 1 diabetic children treated with Tregs infusions (n = 10) during follow-up. Values for matched comparison patients not treated with Tregs (n = 10) are shown as gray columns. Values are given as median (minimum–maximum). *Significant differences.

Figure 2

Levels of CD3⁺CD4⁺CD25^highCD127⁻FoxP3⁺ Tregs in type 1 diabetic children treated with Tregs infusions (n = 10) during follow-up. Value for the −10-days point refers to the day of blood drawing for Tregs sorting. Gray column depicts values measured for the matched comparison patients not treated with Tregs (only six patients were available). Data are shown as medians (minimum–maximum). *Significant differences.