Babak Aghili; Ali Akbar Amirzargar; Asadollah Rajab; Ali Rabbani; Arya Sotoudeh; Sara Assadiasl; Bagher Larijani; Ahmad Massoud
Volume 12, Issue 4 , December 2015, , Pages 240-251
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 ...
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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 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). 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.
Sara Assadiasl; Pedram Ahmadpoor; Mohsen Nafar; Mahboob Lessan Pezeshki; Fateme Pourrezagholi; Mahmoud Parvin; Abtin Shahlaee; Adel Sepanjnia; Mohammad Hossein Nicknam; Aliakbar Amirzargar
Volume 11, Issue 3 , September 2014, , Pages 139-152
Abstract
Background: Regulatory T cells have been suggested to have a protective role against acute rejection in allograft recipients. However, there is little information available about their contribution to chronic rejection process. The role of transforming growth factor-beta 1 (TGF- β1) as a profibrogenic ...
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Background: Regulatory T cells have been suggested to have a protective role against acute rejection in allograft recipients. However, there is little information available about their contribution to chronic rejection process. The role of transforming growth factor-beta 1 (TGF- β1) as a profibrogenic and/or immunoregulatory cytokine in renal allografts is also controversial. Objectives: To evaluate the frequency of CD4+CD25+CD127- and CD3+CD8+CD28- regulatory T cells in chronic allograft dysfunction (CAD) and to investigate the expression of TGF- β1 in renal allografts. Methods: Thirty biopsy-proven CAD patients were pair-matched with 30 stable graft function patients and a third group of healthy volunteers. Flowcytometry was performed on PBMCs to determine the frequency of CD3+CD8+CD28- and CD4+CD25+CD127- regulatory T cells in lymphocyt population. TGF- β1 gene expression was assessed by Real Time PCR. Results: The percentage of CD3+CD8+CD28- Tregs among renal allograft recipients was higher than healthy controls (p<0.001) since stable graft patients showed the most rates. The frequency of CD4+CD25+CD127- Tregs was lower in CAD patients than stable recipients (p=0.024) and healthy group (p=0.015). TGF- β1 gene expression was greater in CAD patients compared to healthy group (p=0.03) but there was no significant difference between gene expression of stable graft patients and healthy volunteers. Conclusion: The negative association between the frequency of regulatory T cell subtypes and chronic allograft dysfunction proposes these cells as probable candidates for promoting allograft survival. Moreover, despite the immunoregulatory capacity of TGF- β1, it is likely to be implicated in chronic damages of allograft tissue.
