Calcineurin inhibitors, but not rapamycin, reduce percentages of CD4+CD25+FOXP3+ regulatory T cells in renal transplant recipients.
BACKGROUND
Immunosuppression in renal transplantation, although manageable in the short-term, is a major hurdle for long-term graft survival. Recently, increased frequencies of CD4CD25 regulatory T cells (Tregs) have been described as an additional mechanism that induces alloimmune tolerance.


METHODS
We assessed 64 renal transplant recipients with stable renal function for at least one year. Patients were divided into two groups according to the immunosuppression they were receiving at the moment of the study: one consisted of patients receiving rapamycin (Rapa) but not calcineurin inhibitors (CNI), and the other group received CNI but not Rapa. The Rapa group was further divided into three subgroups according to their previous experience with CNI: CNI-free, CNI withdrawal, and CNI conversion. Frequencies of blood Tregs were studied by flow cytometry after staining with monoclonal antibodies specific for different markers of Tregs.


RESULTS
Frequencies of CD4 T cells with regulatory phenotype and function were significantly decreased in peripheral blood of renal transplant patients receiving CNI compared with those receiving Rapa. This effect was independent of an early exposure to CNI because the CNI-free patients in the Rapa group showed similar frequencies of Tregs to the CNI withdrawal and CNI conversion groups.


CONCLUSIONS
CNI, but not Rapa, induce a decrease of circulating Tregs in stable renal transplant recipients. Thus, Rapa might be further explored in strategies using preservation of Tregs for transplant tolerance. Furthermore, quantification of blood Tregs may be a suitable tool to identify renal transplant recipients who may be candidates for reduced immunosuppression.
Segundo
David San
DS
Servicios Inmunología, Hospital Universitario Marqués de Valdecilla, Santander, Spain.
Ruiz
Juan Carlos
JC
Izquierdo
María
M
Fernández-Fresnedo
Gema
G
Gómez-Alamillo
Carlos
C
Merino
Ramón
R
Benito
María Jesús
MJ
Cacho
Eva
E
Rodrigo
Emilio
E
Palomar
Rosa
R
López-Hoyos
Marcos
M
Arias
Manuel
M
D000328:Adult; D000368:Aged; D065095:Calcineurin Inhibitors; D005260:Female; D051858:Forkhead Transcription Factors / Q000032:analysis*; D005919:Glomerular Filtration Rate; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D016030:Kidney Transplantation; D007959:Lymphocyte Culture Test, Mixed; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D020123:Sirolimus / Q000494:pharmacology*; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects*; D014184:Transplantation, Homologous
D065095:Calcineurin Inhibitors; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D007166:Immunosuppressive Agents; D020123:Sirolimus