title: Clinical application of regulatory T cells in type 1 diabetes.
abstract: Regulatory T cells (Tregs) are responsible for the maintenance of peripheral tolerance. Animal studies have shown that administration of Tregs can prevent type 1 diabetes (DM1). Several clinical trials attempted to induce Tregs with various agents, and thus provide long-term tolerance of β cells in DM1. Nevertheless, most of these studies have focused on clinical parameters (e.g. C-peptide) and not Treg numbers nor their function after treatment. Therefore, it is not possible to conclude if the majority of these therapies failed because the drugs did not induce Tregs, or if they failed despite Treg expansion. The current knowledge regarding Tregs, along with our experience in Treg therapy of patients with graft versus host disease, prompted us to use ex vivo expanded Tregs in 10 children with recent-onset DM1. No adverse effects in the treated individuals were observed. There was a significant increase in Treg number in peripheral blood immediately after the treatment administration, while the first clinical differences between treated and control patients were observed 4 months after Treg injection. Treated individuals had higher C-peptide levels and lower insulin requirements than non-treated children. Eleven months after diagnosis of DM1, there are still 2 individuals who are independent of exogenous insulin. These results indicate that autologous Tregs are a safe and well-tolerated therapy in children with DM1, which can inhibit or delay the destruction of pancreatic β cells. Additionally, Tregs can be a useful tool for local protection of transplanted pancreatic islets. Isolation and expansion of antigen-specific Tregs is one of the directions for future studies on cellular therapy of DM1.
authors.affiliation: Department of Family Medicine, Medical University of Gdańsk, Gdańsk, Poland. natalia.marek@gumed.edu.pl
authors.forename: Natalia
authors.initials: N
authors.lastname: Marek-Trzonkowska
authors.forename: Małgorzata
authors.initials: M
authors.lastname: Myśliwec
authors.forename: Janusz
authors.initials: J
authors.lastname: Siebert
authors.forename: Piotr
authors.initials: P
authors.lastname: Trzonkowski
mesh_terms: D000328:Adult; D002096:C-Peptide / Q000097:blood; D064987:Cell- and Tissue-Based Therapy; D018834:Chaperonin 60 / Q000276:immunology; D002648:Child; D003922:Diabetes Mellitus, Type 1 / Q000628:therapy*; D006801:Humans; D050417:Insulin-Secreting Cells / Q000187:drug effects / Q000502:physiology; D007376:Interleukin-2 / Q000008:administration & dosage; D010446:Peptide Fragments / Q000276:immunology; D020123:Sirolimus / Q000008:administration & dosage; D050378:T-Lymphocytes, Regulatory / Q000502:physiology* / Q000637:transplantation
chemical_list: D002096:C-Peptide; D018834:Chaperonin 60; C447781:DiaPep 277; D007376:Interleukin-2; D010446:Peptide Fragments; D020123:Sirolimus
keywords: DM1; Tregs; cellular therapy; immunotherapy; β cell preservation