title: Altered Suppressor Function of Regulatory T Cells in Type 1 Diabetes.
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.
  
  
  OBJECTIVE
  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 sex- matched 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 Magnetic-Activated 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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Babak
authors.initials: B
authors.lastname: Aghili
authors.forename: Ali Akbar
authors.initials: AA
authors.lastname: Amirzargar
authors.forename: Asadollah
authors.initials: A
authors.lastname: Rajab
authors.forename: Ali
authors.initials: A
authors.lastname: Rabbani
authors.forename: Arya
authors.initials: A
authors.lastname: Sotoudeh
authors.forename: Sara
authors.initials: S
authors.lastname: Assadiasl
authors.forename: Bagher
authors.initials: B
authors.lastname: Larijani
authors.forename: Ahmad
authors.initials: A
authors.lastname: Massoud
mesh_terms: D000293:Adolescent; D000328:Adult; D015703:Antigens, CD / Q000378:metabolism; D049109:Cell Proliferation; D002469:Cell Separation; D002478:Cells, Cultured; D018920:Coculture Techniques; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology*; D005260:Female; D005434:Flow Cytometry; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation; D006801:Humans; D007108:Immune Tolerance; D008297:Male; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D055815:Young Adult
chemical_list: D015703:Antigens, CD; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors