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Altered Suppressor Function of Regulatory T Cells in Type 1 Diabetes Pubmed



Aghili B1 ; Amirzargar AA1, 2 ; Rajab A3 ; Rabbani A4 ; Sotoudeh A4 ; Assadiasl S1 ; Larijani B5 ; Massoud A1
Authors
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Authors Affiliations
  1. 1. Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Iran
  2. 2. Molecular Immunology Research Center, Tehran University of Medical Sciences, Iran
  3. 3. Department of Endocrinology, Iranian Diabetes Association, Tehran University of Medical Sciences, Children's Medical Center, Iran
  4. 4. Growth and Development Center, Tehran University of Medical Sciences, Children's Medical Center, Iran
  5. 5. Endocrinology and Metabolism Research Center, Tehran University of Medical Sciences, Tehran, Iran

Source: Iranian Journal of Immunology Published:2015


Abstract

Background: Type 1 diabetes (T1D) is a T cell mediated autoimmune disease targeting the insulin-producing β cells within pancreatic islets. Autoimmune diseases may develop as a consequence of altered balance between regulatory (Tregs) and autoreactive T cells. Objectives: To evaluate Treg cells frequency and suppressive function in the peripheral blood of newly diagnosed T1D patients in comparison with healthy controls. Methods: Fifteen new cases of T1D patients and 15 age-and sexmatched healthy controls were recruited to this study. Their peripheral blood mononuclear cells (PBMCs) were isolated and CD4+CD25+FoxP3+CD127-/low Treg cells were studied by flowcytometry technique. Thereafter, Tregs were isolated by MagneticActivated Cell Separation (MACS) technology and by using CFSE (carboxyfluorescein succinimidyl ester) dilution assay, their suppressive activity was evaluated in the coculture of CD4+CD25- T responder cells with Treg cells. Results: The percentage of CD4+CD25+FoxP3+CD127-/low Tregs did not differ between T1D patients and healthy controls but the MFI (mean fluorescence intensity) of transcription factor FoxP3 (forkhead box protein P3) was significantly decreased in T1D patients (20.03 ± 1.4 vs. 31.33 ± 2.95, p=0.0017). Moreover, the suppressive function of CD4+CD25+CD127-/low Treg cells was significantly diminished in T1D patients in comparison with control group (35.16 ± 4.93% vs. 60.45 ± 5.26%, respectively, p=0.0015). Conclusion: Present study indicates an impaired immune regulation among T1D patients, characterized by defects in suppressive function and expression of FoxP3 in Treg cells without any significant decrease in their frequency in peripheral blood. © 2015, Shiraz University of Medical Sciences. All rights reserved.