Regulatory T Cell Subtypes and TGF-β1 Gene Expression in Chronic Allograft Dysfunction

Abstract

<b>Background</b>: <span>Regulatory T cells have been suggested to have a protective role against</span> 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- <span lang="JA">β</span><span>1) as a profibrogenic and/or immunoregulatory cytokine in renal</span> allografts is also controversial. <span><br/><b>Objectives</b>: </span><span>To evaluate the frequency of</span> CD4+CD25+CD127- and CD3+CD8+CD28- regulatory T cells in chronic allograft dysfunction (CAD) and to investigate the expression of TGF- <span lang="JA">β</span><span>1 in renal allografts.</span> <br/><b>Methods</b>: <span>Thirty biopsy-proven CAD patients were pair-matched with 30 stable graft</span> 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- <span lang="JA">β</span><span>1 gene expression was assessed by</span> Real Time PCR. <span><br/><b>Results</b>: </span><span>The percentage of CD3+CD8+CD28- Tregs among renal</span> 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- <span lang="JA">β</span><span>1 gene</span> 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. <span><br/><b>Conclusion</b>: </span><span>The negative association between the frequency of</span> 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- <span lang="JA">β</span><span>1, it is likely to be implicated in chronic damages</span> of allograft tissue.