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

Diabetes Care. 2012 Sep;35(9):1817-20. doi: 10.2337/dc12-0038. Epub 2012 Jun 20.

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.

Publication types

  • Clinical Trial

MeSH terms

  • Adolescent
  • CD4-Positive T-Lymphocytes / cytology
  • CD4-Positive T-Lymphocytes / metabolism*
  • CD4-Positive T-Lymphocytes / physiology*
  • Child
  • Diabetes Mellitus, Type 1 / pathology
  • Diabetes Mellitus, Type 1 / physiopathology*
  • Diabetes Mellitus, Type 1 / therapy*
  • Female
  • Humans
  • Insulin-Secreting Cells / metabolism
  • Insulin-Secreting Cells / physiology*
  • Interleukin-2 Receptor alpha Subunit / metabolism*
  • Interleukin-7 Receptor alpha Subunit / metabolism*
  • Male
  • T-Lymphocytes, Regulatory / cytology
  • T-Lymphocytes, Regulatory / metabolism*
  • T-Lymphocytes, Regulatory / physiology*

Substances

  • Interleukin-2 Receptor alpha Subunit
  • Interleukin-7 Receptor alpha Subunit