The changes in CD4+CD25high T cells and TGFβ1 levels in different stages of adult-onset Type 1 diabetes

Stages in T1D: differences in CD25high T cells and TGFβ1

  • Tanja Miličić Medicinski fakultet UB, Klinika za endokrinologiju, dijabetes i bolesti metabolizma UKCS
  • Aleksandra Jotic Clinic for Endocrinology, Diabetes and Metabolic Diseases, University Clinical Centre of Serbia, Faculty of Medicine, University of Belgrade, Dr Subotica 13, 11000 Belgrade, Serbia
  • Ivanka Markovic Clinic for Endocrinology, Diabetes and Metabolic Diseases, University Clinical Centre of Serbia, Faculty of Medicine, University of Belgrade, Dr Subotica 13, 11000 Belgrade, Serbia
  • Dusan Popadic Clinic for Endocrinology, Diabetes and Metabolic Diseases, University Clinical Centre of Serbia, Faculty of Medicine, University of Belgrade, Dr Subotica 13, 11000 Belgrade, Serbia
  • Katarina Lalic Clinic for Endocrinology, Diabetes and Metabolic Diseases, University Clinical Centre of Serbia, Faculty of Medicine, University of Belgrade, Dr Subotica 13, 11000 Belgrade, Serbia
  • Veljko Uskokovic Clinic for Endocrinology, Diabetes and Metabolic Diseases, University Clinical Centre of Serbia, Faculty of Medicine, University of Belgrade, Dr Subotica 13, 11000 Belgrade, Serbia
  • Ljiljana Lukic Clinic for Endocrinology, Diabetes and Metabolic Diseases, University Clinical Centre of Serbia, Faculty of Medicine, University of Belgrade, Dr Subotica 13, 11000 Belgrade, Serbia
  • Marija Macesic Clinic for Endocrinology, Diabetes and Metabolic Diseases, University Clinical Centre of Serbia, Faculty of Medicine, University of Belgrade, Dr Subotica 13, 11000 Belgrade, Serbia
  • Jelena Stanarcic Clinic for Endocrinology, Diabetes and Metabolic Diseases, University Clinical Centre of Serbia, Faculty of Medicine, University of Belgrade, Dr Subotica 13, 11000 Belgrade, Serbia
  • Milica Stoiljkovic Clinic for Endocrinology, Diabetes and Metabolic Diseases, University Clinical Centre of Serbia, Faculty of Medicine, University of Belgrade, Dr Subotica 13, 11000 Belgrade, Serbia
  • Mina Milovancevic Clinic for Endocrinology, Diabetes and Metabolic Diseases, University Clinical Centre of Serbia, Faculty of Medicine, University of Belgrade, Dr Subotica 13, 11000 Belgrade, Serbia
  • Djurdja Rafailovic Clinic for Endocrinology, Diabetes and Metabolic Diseases, University Clinical Centre of Serbia, Faculty of Medicine, University of Belgrade, Dr Subotica 13, 11000 Belgrade, Serbia
  • Aleksandra Bozovic Clinic for Endocrinology, Diabetes and Metabolic Diseases, University Clinical Centre of Serbia, Faculty of Medicine, University of Belgrade, Dr Subotica 13, 11000 Belgrade, Serbia
  • Nina Radisavljevic Clinic for Endocrinology, Diabetes and Metabolic Diseases, University Clinical Centre of Serbia, Faculty of Medicine, University of Belgrade, Dr Subotica 13, 11000 Belgrade, Serbia
  • Nebojsa Lalic Clinic for Endocrinology, Diabetes and Metabolic Diseases, University Clinical Centre of Serbia, Faculty of Medicine, University of Belgrade, Dr Subotica 13, 11000 Belgrade, Serbia
DOI: https://doi.org/10.5937/jomb0-49868
Keywords: CD4 CD25high T cells, first-degree relatives of patients with type 1 diabetes, TGFβ, type 1 diabetes

Abstract


Background. Previous studies suggested important role of impairments in T cells subsets in different stages during type 1 diabetes (T1D) development, while data regarding CD25high T cells and transforming growth factor β1-TGFβ1, both T regulatory associated, still remains controversial. We analysed the level of (a) CD25high T cells (b) TGFβ1 in 17 first-degree relatives of patients with T1D in stage 1 (FDRs1) (GADA+, IA-2+); 34 FDRs in stage 0 (FDRs0) (GADA-, IA-2-); 24 recent-onset T1D in insulin requiring state (IRS); 10 patients in clinical remission (CR); 18 healthy, unrelated controls (CTR). Methods. T cell subsets were characterized by two-color immunofluorescence staining and flow cytometry, TGFβ1 was determined by ELISA, GADA, and IA-2 by RIA. Results. The level of CD25high T cells in FDRs1 was lower than controls, FDRs0, IRS, and CR (p<0.001). Additionally, the cut-off point for CD25high = 1.19%, with a probability of 0.667, for having a higher risk for T1D. TGFβ1 level in FDRs1, FDRs0, IRS, and CR, was lower than controls (p<0.001). IRS has a higher TGFβ1 level than CR (p<0.001). Conclusions. Stage 1, a higher risk for T1D, is characterized by decreases in CD25high T cells and TGFβ1, partially reflecting impaired T regulatory response, implying that changes of this T cells subset might be a risk marker for T1D. FDRs irrespective of risk for T1D and T1D patients irrespective of state, had depletion of TGFβ1, suggesting the association of TGFβ1 with familiar risk and manifestation of T1D. Furthermore, clinical course of overt T1D might be modulated on TGFβ1 level.

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Published
2024/07/04
Issue
Ahead of print
Section
Original paper

Copyright (c) 2024 Tanja Miličić, Aleksandra Jotic, Ivanka Markovic, Dusan Popadic, Katarina Lalic, Veljko Uskokovic, Ljiljana Lukic, Marija Macesic, Jelena Stanarcic, Milica Stoiljkovic, Mina Milovancevic, Djurdja Rafailovic, Aleksandra Bozovic, Nina Radisavljevic, Nebojsa Lalic

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