Generation of T regulatory cells in children with type 1 diabetes mellitus Generacja komórek T regulatorowych u dzieci z cukrzyc typu 1

Introduction: In spite of intensive research the pathogenesis of type 1 diabetes mellitus is not thoroughly understood. One of the ideas which currently has a great number of supporters is the theory of the participation of T regulatory cells in the mechanism of insufficient suppression of the immune response against pancreatic self -antigens. According to some authors, the infusion of T regulatory cells in autoimmune diseases could lead to long -term remission or even a complete cure. Aim of the study: The aim of our present study was to achieve T regulatory cells from conventional T lymphocytes isolated from a small amount of peripheral blood in children with type 1 diabetes mellitus and their comparison to the Tregs generated from the blood of control children. Additionally, we assessed the changes in the expression of selected genes essential for the function of these cells during Tregs generation. Material and methods: The examined group consisted of 20 children with type 1 diabetes mellitus, the control group consisted of 20 non -diabetic children. From the peripheral blood CD4+CD25 - cells were separated and cultured with T -reg expander and interleukin (IL) 2. Before and after the culture the cells were analysed according to the expression of transcription factor FoxP3 and other molecules/cytokines: OX40, 4 -1BB, GITR, ICOS -1, CTLA -4 and IFN -γ, IL -10 and TGF -β. Results: We observed a significantly higher percentage of T regulatory cells after the culture (with no difference between diabetic and control children). Moreover, we observed a lower expression of mRNA for GITR molecule and a higher IL -10 expression in the cultures of diabetic children compared to the control ones. The cells cultured from the blood of control children were characterised by a higher increase in the expression of mRNA for ICOS -1 and a lower expression of mRNA for TGF -β in comparison to the cultures from diabetic children. Conclusions: The results of our investigations confirm the possibility of generating T regulatory cells from conventional T lymphocytes from peripheral blood of children with newly recognised type 1 diabetes mellitus.