TY - JOUR T1 - Proinsulin-specific T regulatory cells may control immune responses in type 1 diabetes: implications for adoptive therapy JF - BMJ Open Diabetes Research & Care JO - BMJ Open Diab Res Care DO - 10.1136/bmjdrc-2019-000873 VL - 8 IS - 1 SP - e000873 AU - Mateusz Gliwiński AU - Dorota Iwaszkiewicz-Grześ AU - Anna Wołoszyn-Durkiewicz AU - Monika Tarnowska AU - Magdalena Żalińska AU - Matylda Hennig AU - Hanna Zielińska AU - Anna Dukat-Mazurek AU - Joanna Zielkowska-Dębska AU - Maciej Zieliński AU - Anna Jaźwińska-Curyłło AU - Radosław Owczuk AU - Przemysława Jarosz-Chobot AU - Artur Bossowski AU - Agnieszka Szadkowska AU - Wojciech Młynarski AU - Natalia Marek-Trzonkowska AU - Grażyna Moszkowska AU - Janusz Siebert AU - Małgorzata Myśliwiec AU - Piotr Trzonkowski Y1 - 2020/02/01 UR - http://drc.bmj.com/content/8/1/e000873.abstract N2 - Objective Here we looked for possible mechanisms regulating the progression of type 1 diabetes mellitus (T1DM). In this disease, autoaggressive T cells (T conventional cells, Tconvs) not properly controlled by T regulatory cells (Tregs) destroy pancreatic islets.Research design and methods We compared the T-cell compartment of patients with newly diagnosed T1DM (NDT1DM) with long-duration T1DM (LDT1DM) ones. The third group consisted of patients with LDT1DM treated previously with polyclonal Tregs (LDT1DM with Tregs). We have also looked if the differences might be dependent on the antigen specificity of Tregs expanded for clinical use and autologous sentinel Tconvs.Results Patients with LDT1DM were characterized by T-cell immunosenescence-like changes and expansion of similar vβ/T-cell receptor (TCR) clones in Tconvs and Tregs. The treatment with Tregs was associated with some inhibition of these effects. Patients with LDT1DM possessed an increased percentage of various proinsulin-specific T cells but not GAD65-specific ones. The percentages of all antigen-specific subsets were higher in the expansion cultures than in the peripheral blood. The proliferation was more intense in proinsulin-specific Tconvs than in specific Tregs but the levels of some proinsulin-specific Tregs were exceptionally high at baseline and remained higher in the expanded clinical product than the levels of respective Tconvs in sentinel cultures.Conclusions T1DM is associated with immunosenescence-like changes and reduced diversity of T-cell clones. Preferential expansion of the same TCR families in both Tconvs and Tregs suggests a common trigger/autoantigen responsible. Interestingly, the therapy with polyclonal Tregs was associated with some inhibition of these effects. Proinsulin-specific Tregs appeared to be dominant in the immune responses in patients with T1DM and probably associated with better control over respective autoimmune Tconvs.Trial registration number EudraCT 2014-004319-35. ER -