title: Calcineurin inhibitors affect circulating regulatory T cells in stable renal transplant recipients.
abstract: BACKGROUND
  Immunosuppression, although crucial for short-term management, has been described in renal transplantation to be a major hurdle for long-term graft survival. Efforts have been directed at achieving a true state of allotolerance, thereby reducing the load of immunosuppression. Recently, increased frequencies of CD4(+)CD25(high) regulatory T cells (Tregs) have been described as an additional mechanism to induce alloimmune tolerance.
  
  
  METHODS
  We assessed 64 renal transplant recipients with stable renal function for at least 1 year, divided into two groups: one composed of patients receiving rapamycin but not calcineurin inhibitors (CNIs), and another, of those receiving CNIs but not rapamycin.
  
  
  RESULTS
  We demonstrated that T cells with a regulatory phenotype were decreased in peripheral blood of renal transplant recipients under CNI therapy compared to those who were CNI-free. The Tregs in our patients showed a modest association with renal function as measured by the delta serum creatinine, which was not significant.
  
  
  CONCLUSIONS
  CNIs, but not rapamycin, reduce the frequencies of circulating Tregs in renal transplant recipients. The use of rapamycin might be further exploited in strategies reducing immunosuppression in renal transplantation. Furthermore, quantification of blood Tregs may be a suitable tool to identify those recipients who are candidates for reducing immunosuppression.
authors.affiliation: Servicios de Inmunología, Hospital Universitario Marqués de Valdecilla, Santander, Spain.
authors.forename: D
authors.initials: D
authors.lastname: San Segundo
authors.forename: J C
authors.initials: JC
authors.lastname: Ruiz
authors.forename: G
authors.initials: G
authors.lastname: Fernández-Fresnedo
authors.forename: M
authors.initials: M
authors.lastname: Izquierdo
authors.forename: C
authors.initials: C
authors.lastname: Gómez-Alamillo
authors.forename: E
authors.initials: E
authors.lastname: Cacho
authors.forename: M J
authors.initials: MJ
authors.lastname: Benito
authors.forename: E
authors.initials: E
authors.lastname: Rodrigo
authors.forename: R
authors.initials: R
authors.lastname: Palomar
authors.forename: M
authors.initials: M
authors.lastname: López-Hoyos
authors.forename: M
authors.initials: M
authors.lastname: Arias
mesh_terms: D000328:Adult; D065095:Calcineurin Inhibitors; D005260:Female; D006650:Histocompatibility Testing; D006801:Humans; D016130:Immunophenotyping; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D016030:Kidney Transplantation / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D020123:Sirolimus / Q000627:therapeutic use*; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*
chemical_list: D065095:Calcineurin Inhibitors; D007166:Immunosuppressive Agents; D020123:Sirolimus