Therapy of type 1 diabetes with CD4(+)CD25(high)CD127-regulatory T cells prolongs survival of pancreatic islets - results of one year follow-up.
It is hypothesized that CD4(+)CD25(+)FoxP3(+) regulatory T cells (Tregs) can prevent destruction of pancreatic islets protecting from type 1 diabetes (DM1). Here we present results of one year follow-up of 12 DM1 children treated with autologous expanded ex vivo Tregs. Patients received either a single or double Tregs infusion up to the total dose of 30×10(6)/kg. No severe adverse effects were observed. The treatment did not impair post-immunization antibody responses. Tregs infusion was followed by increase in Tregs number in peripheral blood. Most of the patients responded to the therapy with increase in C-peptide levels (8/12 and 4/6 after the first and the second dose, respectively). Tregs administration resulted also in lower requirement for exogenous insulin (8/12 treated patients versus 2/10 untreated controls in remission) with two children completely insulin independent at one year. Repetitive administration of Tregs is safe and can prolong survival of β-cells in DM1 (registration: ISRCTN06128462).
Department of Family Medicine, Medical University of Gdańsk, Dębinki 2, 80-210 Gdańsk, Poland.
Natalia
N
Marek-Trzonkowska
Department of Pediatric Diabetology and Endocrinology, Medical University of Gdańsk, Dębinki 7, 80-210 Gdańsk, Poland.
Małgorzata
M
Myśliwiec
Department of Clinical Immunology and Transplantology, Medical University of Gdańsk, Dębinki 7, 80-210 Gdańsk, Poland.
Anita
A
Dobyszuk
Department of Clinical Immunology and Transplantology, Medical University of Gdańsk, Dębinki 7, 80-210 Gdańsk, Poland.
Marcelina
M
Grabowska
Department of Pediatric Diabetology and Endocrinology, Medical University of Gdańsk, Dębinki 7, 80-210 Gdańsk, Poland.
Ilona
I
Derkowska
Regional Center of Blood Donation and Treatment, Hoene-Wrońskiego, 180-210, Gdańsk, Poland.
Jolanta
J
Juścińska
Department of Anesthesiology and Critical Care, Medical University of Gdańsk, Dębinki 7, 80-210 Gdańsk, Poland.
Radosław
R
Owczuk
Department of Pediatrics, Oncology, Hematology and Diabetology, Medical University of Łódź, Sporna 36/50, 91-738 Łódź, Poland.
Agnieszka
A
Szadkowska
Department of Surgery, Section of Transplantation, The University of Chicago, 5841 S. Maryland Ave. MC5027, Chicago, 60637 IL, USA.
Piotr
P
Witkowski
Department of Pediatrics, Oncology, Hematology and Diabetology, Medical University of Łódź, Sporna 36/50, 91-738 Łódź, Poland.
Wojciech
W
Młynarski
Department of Pediatrics, Endocrinology and Diabetes, Medical University of Silesia, Poniatowskiego 15, 40-055 Katowice, Poland.
Przemysława
P
Jarosz-Chobot
Department of Pediatrics Endocrinology and Diabetology, Medical University of Białystok, Jana Kilińskiego 1, 15-089 Białystok, Poland.
Artur
A
Bossowski
Department of Family Medicine, Medical University of Gdańsk, Dębinki 2, 80-210 Gdańsk, Poland.
Janusz
J
Siebert
Department of Clinical Immunology and Transplantology, Medical University of Gdańsk, Dębinki 7, 80-210 Gdańsk, Poland. Electronic address: ptrzon@gumed.edu.pl.
Piotr
P
Trzonkowski
D000293:Adolescent; D002096:C-Peptide / Q000097:blood; D064987:Cell- and Tissue-Based Therapy / Q000009:adverse effects; D002648:Child; D002675:Child, Preschool; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology* / Q000401:mortality / Q000628:therapy*; D005500:Follow-Up Studies; D006801:Humans; D053645:Interleukin-2 Receptor alpha Subunit; D053699:Interleukin-7 Receptor alpha Subunit; D016381:Islets of Langerhans Transplantation / Q000009:adverse effects; D012307:Risk Factors; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000637:transplantation*; D016896:Treatment Outcome
D002096:C-Peptide; D053645:Interleukin-2 Receptor alpha Subunit; D053699:Interleukin-7 Receptor alpha Subunit
CD4+CD25+ T regulatory cells; Immunotherapy; Tregs; Type 1 diabetes mellitus