Document Type : Original Article

Authors

• Sara Assadiasl ^{1, 2}
• Pedram Ahmadpoor ³
• Mohsen Nafar ³
• Mahboob Lessan Pezeshki ⁴
• Fateme Pourrezagholi ³
• Mahmoud Parvin ⁵
• Abtin Shahlaee ²
• Adel Sepanjnia ¹
• Mohammad Hossein Nicknam ^{1, 2}
• Aliakbar Amirzargar ^{1, 2}

¹ Department of Immunology, School of Medicine

² Molecular Immunology Research Center, Tehran University of Medical Sciences

³ Chronic Kidney Disease Research Center, Labbafinejad Hospital, Shahid Beheshti University of Medical Sciences

⁴ Nephrology Research Center, Tehran University of Medical Sciences

⁵ Department of Pathology, Labbafinejad Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran

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 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.

Keywords

• Chronic Allograft Dysfunction
• Regulatory T cells
• TGF-β1