Different immunosuppressive combinations on T-cell regulation in renal transplant recipients.
OBJECTIVE
Recent studies indicate that regulatory T-cells (Tregs) promote transplant tolerance. We studied Treg levels in 39 stable renal transplant recipients to determine the sizes of the Treg populations and the effects of treatment regimens thereof.


METHODS
All patients (19 with good graft function and 20 with chronic allograft nephropathy) received induction therapy (basiliximab) and were on triple immunosuppressive regimens with calcineurin inhibitors (cyclosporine or tacrolimus), mycophenolate mofetil (MMF) or everolimus and steroids. Twenty healthy subjects served as controls. Whole blood samples were stained with anti-CD4, CD25, CD127, and FoxP3 antibodies and analyzed by flow cytometry to determine CD4+CD25(high)FoxP3+/- and CD4+ CD25(high)CD127(-/low) Treg levels.


RESULTS
All patients had significantly reduced CD4+CD25(high)FoxP3+/- but no CD4+ CD25(high)CD127(-/low) Treg levels compared to controls. Renal allograft function did not correlate with Treg levels. Statistically significant correlations between CD4+CD25(high)Foxp3+ Tregs and tacrolimus levels and CD4+CD25(high)Foxp3- Tregs and HLA-DR mismatching were detected. Patients receiving MMF had significantly higher CD4+CD25(high)Foxp3+ Tregs compared to patients on everolimus who were also receiving lower doses of calcineurin inhibitors.


CONCLUSIONS
Overall, immunosuppression lowers CD4+CD25(high)FoxP3+/- Treg levels significantly in the periphery in renal transplant recipients. In addition, different immunosuppressive regimens have different impacts on CD4+CD25(high)FoxP3+ Tregs, a fact that may influence long-term allograft survival.
Fourtounas
Costas
C
Department of Internal Medicine, Division of Nephrology, Medical School and University Hospital, Patras, Greece.
Dousdampanis
Periklis
P
Sakellaraki
Panagiota
P
Rodi
Maria
M
Georgakopoulos
Tassos
T
Vlachojannis
Jannis G
JG
Mouzaki
Athanasia
A
D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D000077552:Basiliximab; D016572:Cyclosporine / Q000008:administration & dosage; D004359:Drug Therapy, Combination; D000068338:Everolimus; D005260:Female; D006084:Graft Rejection / Q000188:drug therapy* / Q000276:immunology; D006801:Humans; D016130:Immunophenotyping; D007166:Immunosuppressive Agents / Q000008:administration & dosage*; D016030:Kidney Transplantation / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage; D020123:Sirolimus / Q000008:administration & dosage / Q000031:analogs & derivatives; D013256:Steroids / Q000008:administration & dosage; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects* / Q000276:immunology; D016559:Tacrolimus / Q000008:administration & dosage; D055815:Young Adult
D000911:Antibodies, Monoclonal; D007166:Immunosuppressive Agents; D011993:Recombinant Fusion Proteins; D013256:Steroids; D016572:Cyclosporine; D000077552:Basiliximab; D000068338:Everolimus; D009173:Mycophenolic Acid; D020123:Sirolimus; D016559:Tacrolimus