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Immune reactivity of renal transplant recipients receiving humanized anti-CD25 monoclonal antibodies during the early posttransplant period

Background: Immunosuppression should be applied according to the individual needs of renal allograft recipients. Methods of immune monitoring have been investigated to avoid complications of over- or underimmunosuppression. Methods: This prospective randomized trial included thirty renal allograft recipients in our center from 2006 until 2008. All patients received daclizumab in combination with mycophenolate mofetil, corticosteroids and a calcineurin inhibitor. Daclizumab was administered at a dosage of 1 mg/kg BW immediately before transplantation and every 15±1 days. During the first six weeks after transplantation the anti-CD3-stimulated proliferative response of peripheral blood T-lymphocytes (PBTL) was followed by cell cycle analysis. The proportion of PBTL in different phases of the cell cycle and the expression of interleukin-2 receptors (IL-2R) were analyzed by flow-cytometry. Results: As an effect of quadruple immunosuppressive therapy, including daclizumab, cell cycle analysis showed a step-wise decrease of the proliferative response of PBTL during the first six weeks after renal transplantation. A sudden drop in the proportion of IL-2R-positive cells was observed immediately after the first dose of daclizumab, and a significant antiproliferative effect on PBTL after the second dose two weeks after transplantation. In vitro, daclizumab inhibited dose-dependently, the anti-CD3 stimulated proliferation of PBTL of healthy blood donors. Conclusions: These results contribute to the knowledge about the effects of immunosuppressive drugs. Analysis of the immune reactivity of renal allograft recipients by cell-cycle analysis may represent a valuable tool for the immunological follow-up of renal transplant recipients and for the optimization of immunosuppressive treatment, in order to improve patient and graft survival.

Immunosuppression; Renal graft transplantation; Proliferative response of lymphocytes; Anti-CD3; Cell cycle analysis; Flow Cytometry

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