Intragraft Levels of Foxp3 mRNA Predict Progression in Renal Transplants with Borderline Change

Does Borderline Kidney Allograft Rejection Always Require Treatment?

“…Our findings are in line with the report of Mansour et al (5) who found in patients with borderline change histology higher intragraft Foxp3 transcripts in nonprogressors than in progressors and also with the report of Muthukumar et al (4) who found significantly higher Foxp3 mRNA levels in urine samples of patients with successful reversal of ARE than in patients without reversal, and the recent article by Sakamoto et al (11) who observed low Foxp3 mRNA levels in PBL samples of patients with ARE within 60 days after living-donor liver transplantation. Braudeau et al (12) described a decreased number of CD4 ϩ CD25high Foxp3 ϩ T cells among patients with chronic rejection when compared with patients with graft acceptance.…”

“…There is increasing evidence that regulatory CD4 ϩ CD25 ϩ T lymphocytes (Tregs), which have been shown to prevent the activation and proliferation of autoreactive and alloreactive T cells (2), are involved in the pathogenesis of Bord-R through partial inhibition of the graft-damaging action of cytotoxic T cells (CTLs) (3)(4)(5). Forkhead box P3 (Foxp3), which encodes the X-linked forkhead-winged helix transcription factor, was identified as a key regulatory gene required for the development and functional activity of Tregs (6).…”

“…We reported recently that renal transplant recipients with longterm stable allograft function had significantly higher Foxp3 transcripts in their peripheral blood lymphocytes (PBLs) than patients with chronic rejection (7). Wang et al (3) observed an inverse relationship between Foxp3-expressing Treg infiltrates and ARE in a mouse model, and analyzing human biopsy samples, Mansour et al (5) found that intragraft levels of Foxp3 mRNA predict progression of allograft rejection in renal transplants with borderline histologic change.…”

Regulation of the CD4+ T cell allo-immune response by endothelial cells

“…The Treg subset has been implicated in many murine models of allo-specific tolerance [30][31][32]. In humans, several studies have shown that their intra-graft localization was associated with a local reduction of the effector allo-immune response, improved graft survival and a decreased incidence of acute rejection [33][34][35][36]. These data show that the allogeneic CD4 + T cell response is more complex than the over-simplified notion of a Th1-Th2 balance and suggest an equilibrium between effector responses involving Th1, Th2 and Th17 cells implicated in graft rejection and regulatory responses involving Treg cells, implicated in tolerance and thereby promoting graft survival.…”

FOXP3-Positive Regulatory T Cells and Kidney Allograft Tolerance

“…Several studies have tried to assess if a direct relationship exists between good kidney allograft outcome versus onset of rejection. The presence of intragraft Tregs has been suggested as a positive predictor of favorable graft outcome in stable patients under an immunosuppression regimen (65–67), especially with subclinical signs of rejection (65). Bestard and colleagues also showed a correlation between Treg infiltrates and a greater Treg/CD3 + T cell ratio with better graft function 2- to 3-year posttransplantation.…”