title: Sirolimus did not affect CD4(+)CD25(high) forkhead box p3(+)T cells of peripheral blood in renal transplant recipients.
abstract: BACKGROUND
  To achieve a true state of allo-tolerance is one of the ultimate goals in transplantation. Many studies suggest that CD4(+)CD25(high) T regulatory cells (Tregs) have a crucial role to down-regulate the immune response to allo-antigens. In this study, we investigated the possible influence of immunosuppressive therapy, including sirolimus (SRL) and calcineurin inhibitors (CNIs, tacrolimus, or cyclosporine), on the level of Tregs in renal allograft recipients.
  
  
  METHODS
  We assessed 88 renal transplant recipients with stable renal function for at least 2 years, dividing them into 2 groups: SRL-treated (n = 28) or CNIs-treated (n = 29 tacrolimus and n = 31 cyclosporine). Thirty-eight age-matched healthy subjects (HS) served as normal controls. We examined the expression of CD4, CD25, and forkhead box p3 (Foxp3) in peripheral blood mononuclear cells. Flow cytometry was performed with data analysis using Cell Quest software. The 5-year graft survivals were correlated with Tregs content.
  
  
  RESULTS
  CNIs significantly decreased the percentage of Tregs compared with the HS and SRL groups (P < .01). The percentage of Tregs in the SRL group was not significantly different from that among HS. The ratio of CD4(+)CD25(high)Tregs to CD4(+) T cells was 0.88% (0.28-1.42%), 1.15% (0.57-1.48%), and 0.21% (0.11-0.29%) among the SRL, HS, and CNIs cohorts respectively (SRL vs CNIs, P = .000165; SRL vs HS, P = .258; CNIs vs HS, P = .00030). Foxp3 was expressed in >95% of CD4(+)CD25(high) T cells versus <20% among CD4(+)CD25(low) T cells and not at all in CD4(+)CD25(-) T cells. Five-year graft survivals showed no difference between the 2 cohorts (P > .05), and was not correlated with the level of CD4(+)CD25(high) T cells.
  
  
  CONCLUSIONS
  Various immunosuppressive therapies may show different roles in tolerance induction. The present findings suggest that SRL facilitates the induction of CD4(+)CD25(high) T cells, whereas CNIs hamper their development. Graft success for 5 years did not correlate with the level of these putative regulatory cells.
authors: Tianjin First Central Hospital, Abdominal Imaging and Transplant Unit, Tianjin, China.
authors: Z-Q
authors: ZQ
authors: Chu
authors: Q
authors: Q
authors: Ji
mesh_terms: D000328:Adult; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology*; D016022:Case-Control Studies; D005260:Female; D005434:Flow Cytometry; D051858:Forkhead Transcription Factors / Q000378:metabolism*; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D053645:Interleukin-2 Receptor alpha Subunit / Q000378:metabolism*; D007676:Kidney Failure, Chronic / Q000097:blood / Q000188:drug therapy* / Q000601:surgery; D016030:Kidney Transplantation / Q000379:methods*; D007963:Leukocytes, Mononuclear / Q000166:cytology; D008297:Male; D008875:Middle Aged; D020123:Sirolimus / Q000627:therapeutic use*; D014184:Transplantation, Homologous; D016896:Treatment Outcome
chemical_list: C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D007166:Immunosuppressive Agents; D053645:Interleukin-2 Receptor alpha Subunit; D020123:Sirolimus