PURPOSE: 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.
PURPOSE: 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: T Haba; K Uchida; A Katayama; Y Tominaga; T Sato; I Watanabe; H Inagaki; T Kimata; K Goto; K Morozumi; A Takeda; S Takahara; K Takahashi; S Oshima Journal: Transplant Proc Date: 2001 Nov-Dec Impact factor: 1.066
Authors: J Strehlau; M Pavlakis; M Lipman; M Shapiro; L Vasconcellos; W Harmon; T B Strom Journal: Proc Natl Acad Sci U S A Date: 1997-01-21 Impact factor: 11.205
Authors: Richard Kowalski; Diane Post; Mary C Schneider; Judith Britz; Judy Thomas; Mark Deierhoi; Andrew Lobashevsky; Robert Redfield; Eugene Schweitzer; Alonso Heredia; Elise Reardon; Charles Davis; Carol Bentlejewski; John Fung; Ron Shapiro; Adriana Zeevi Journal: Clin Transplant Date: 2003-04 Impact factor: 2.863