Administration of CD4+CD25highCD127− Regulatory T Cells Preserves β-Cell Function in Type 1 Diabetes in Children
- Natalia Marek-Trzonkowska, VMD, PHD1,
- MaŁgorzata Myśliwiec, MD, PHD2,
- Anita Dobyszuk, MSC1,
- Marcelina Grabowska, MSC1,
- Ilona Techmańska, MD2,
- Jolanta Juścińska, MD, PHD3,
- Magdalena A. Wujtewicz, MD, PHD4,
- Piotr Witkowski, MD, PHD5,
- Wojciech MŁynarski, MD, PHD6,
- Anna Balcerska, MD, PHD2,
- Jolanta Myśliwska, MD, PHD7 and
- Piotr Trzonkowski, MD, PHD1,8⇓
- 1Department of Clinical Immunology and Transplantology, Medical University of Gdańsk, Gdańsk, Poland
- 2Department of Pediatrics, Hematology, Oncology, and Endocrinology, Medical University of Gdańsk, Gdańsk, Poland
- 3Blood Bank of the Pomerania Region, Gdańsk Unit, Gdańsk, Poland
- 4Department of Anesthesiology and Critical Care, Medical University of Gdańsk, Gdańsk, Poland
- 5Department of Surgery, Section of Transplantation, University of Chicago, Chicago, IL
- 6Department of Pediatrics, Oncology, Hematology, and Diabetology, Medical University of Lodz, Lodz, Poland
- 7Department of Immunology, Medical University of Gdańsk, Gdańsk, Poland
- 8Tricity Academic Experimental Facility, Medical University of Gdańsk, Gdańsk, Poland
- Corresponding author: Piotr Trzonkowski, .
N.M.-T. and M.M. contributed equally to this study.
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 × 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.
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 Treg 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.
- Received January 6, 2012.
- Accepted April 3, 2012.
- © 2012 by the American Diabetes Association.
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