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


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.
Department of Clinical Immunology and Transplantology, Medical University of Gdansk, Gdansk,Poland.
Natalia
N
Marek-Trzonkowska
Malgorzata
M
Mysliwiec
Anita
A
Dobyszuk
Marcelina
M
Grabowska
Ilona
I
Techmanska
Jolanta
J
Juscinska
Magdalena A
MA
Wujtewicz
Piotr
P
Witkowski
Wojciech
W
Mlynarski
Anna
A
Balcerska
Jolanta
J
Mysliwska
Piotr
P
Trzonkowski
D000293:Adolescent; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000378:metabolism* / Q000502:physiology*; D002648:Child; D003922:Diabetes Mellitus, Type 1 / Q000473:pathology / Q000503:physiopathology* / Q000628:therapy*; D005260:Female; D006801:Humans; D050417:Insulin-Secreting Cells / Q000378:metabolism / Q000502:physiology*; D053645:Interleukin-2 Receptor alpha Subunit / Q000378:metabolism*; D053699:Interleukin-7 Receptor alpha Subunit / Q000378:metabolism*; D008297:Male; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000378:metabolism* / Q000502:physiology*
D053645:Interleukin-2 Receptor alpha Subunit; D053699:Interleukin-7 Receptor alpha Subunit