title: Immune reactivity of renal transplant recipients receiving interleukin-2 receptor antagonists during the early posttransplant period.
abstract: OBJECTIVE
  There is a need for methods that would enable monitoring of the effects of immunosuppression on the recipient's immune system to avoid rejection, immunodeficiency-related complications and non-immune toxicities of the drugs used in therapy.
  
  
  METHODS
  This prospective trial included thirty patients who underwent renal transplantation in our center. All patients received an interleukin-2 receptor (IL-2R) antagonist in combination with mycophenolate, corticosteroid and calcineurin inhibitor. During the first 6 weeks after transplantation, the anti-CD3-stimulated proliferative response of peripheral blood T lymphocytes (PBTL) was studied by cell cycle analysis. The proportion of PBTL in different phases of the cell cycle and expression of IL-2R were determined by flow cytometry.
  
  
  RESULTS
  As an effect of quadruple immunosuppressive therapy including IL-2R antagonists, cell cycle analysis showed an incremental decrease in the proliferative response of PBTL during the first 6 weeks after renal transplantation. A sudden drop in the proportion of IL-2R-positive cells was observed immediately after the first dose of the IL-2R antagonist and a significant antiproliferative effect on PBTL after the second dose. In vitro, IL-2R antagonists showed a dose-dependent inhibition of the anti-CD3-stimulated proliferation of PBTL of healthy blood donors.
  
  
  CONCLUSIONS
  Cell cycle analysis of the immune reactivity of renal allograft recipients may represent a valuable tool for the immunological posttransplant follow-up and optimization of the immunosuppressive therapy.
authors.affiliation: Department of Nephrology and Dialysis, Department of Internal Medicine, University Hospital Rijeka, School of Medicine, University of Rijeka, Rijeka, Croatia.
authors.forename: Stela
authors.initials: S
authors.lastname: Zivčić-Ćosić
authors.forename: Jasna
authors.initials: J
authors.lastname: Lisjak
authors.forename: Sanjin
authors.initials: S
authors.lastname: Rački
authors.forename: Zlatko
authors.initials: Z
authors.lastname: Trobonjača
mesh_terms: D000328:Adult; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage* / Q000494:pharmacology; D017252:CD3 Complex / Q000032:analysis; D065095:Calcineurin Inhibitors; D059447:Cell Cycle Checkpoints / Q000187:drug effects / Q000276:immunology*; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D000077561:Daclizumab; D004359:Drug Therapy, Combination; D005260:Female; D006084:Graft Rejection / Q000517:prevention & control; D006801:Humans; D007074:Immunoglobulin G / Q000008:administration & dosage* / Q000494:pharmacology; D007165:Immunosuppression Therapy / Q000009:adverse effects / Q000379:methods; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000494:pharmacology; D053645:Interleukin-2 Receptor alpha Subunit / Q000032:analysis; D016030:Kidney Transplantation; D018655:Lymphocyte Count; D008297:Male; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives; D011184:Postoperative Period; D011239:Prednisolone / Q000008:administration & dosage; D011446:Prospective Studies; D015375:Receptors, Interleukin-2 / Q000037:antagonists & inhibitors / Q000276:immunology; D013601:T-Lymphocytes / Q000737:chemistry / Q000276:immunology*; D016559:Tacrolimus / Q000008:administration & dosage
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D017252:CD3 Complex; D065095:Calcineurin Inhibitors; D007074:Immunoglobulin G; D007166:Immunosuppressive Agents; D053645:Interleukin-2 Receptor alpha Subunit; D015375:Receptors, Interleukin-2; D011239:Prednisolone; D000077561:Daclizumab; D009173:Mycophenolic Acid; D016559:Tacrolimus