BACKGROUND: Regulatory T cells have been suggested to down-regulate the alloimmune response. The aim of this prospective open study was to evaluate the effects of different inductive agents on peripheral blood regulatory T cells in kidney transplant patients and to analyse their association with short-term graft outcome. METHODS: Regulatory and effector T cell numbers in peripheral blood were determined by flow cytometry in 71 prospectively followed kidney transplant recipients at postoperative day 0, 7, 14, 21, 28, 60 and 90. Patients were treated with a calcineurin inhibitor-based triple immunosuppression with polyclonal rabbit anti-thymocyte globulin (rATG, n = 28), basiliximab, the anti-CD25 monoclonal antibody (n = 18) or without induction (controls, n = 25). Flow cytometry data were correlated to rejection incidence. RESULTS: Compared to controls, CD4(+)CD25(+)FoxP3(+) regulatory T-cell expansion among CD4(+) T cells was noticed in the rATG group at all post-transplant time-points by Day 14 (P < 0.001). A significant decrease in Treg frequency (P < 0.001) and concurrently a transient increase of CD4(+)CD25(low/-)FoxP3(+) population were observed in basiliximab-treated patients 7-60 days post-transplantation. Biopsy-proven acute rejection occurred in 16.7% of controls, 10.7% of the rATG group and in 11.1% of the basiliximab group. Higher CD4(+)FoxP3(+)/CD8(+)CD45RA(+)CD62L(-) ratios were observed repeatedly in those patients after basiliximab induction who were rejection free (P < 0.01). CONCLUSIONS: In this study, the rATG induction therapy was associated with an expansion of regulatory cells. Sustained high CD4(+)FoxP3(+)/Teff ratios were associated with the absence of rejection after basiliximab induction.
BACKGROUND: Regulatory T cells have been suggested to down-regulate the alloimmune response. The aim of this prospective open study was to evaluate the effects of different inductive agents on peripheral blood regulatory T cells in kidney transplant patients and to analyse their association with short-term graft outcome. METHODS: Regulatory and effector T cell numbers in peripheral blood were determined by flow cytometry in 71 prospectively followed kidney transplant recipients at postoperative day 0, 7, 14, 21, 28, 60 and 90. Patients were treated with a calcineurin inhibitor-based triple immunosuppression with polyclonal rabbit anti-thymocyte globulin (rATG, n = 28), basiliximab, the anti-CD25 monoclonal antibody (n = 18) or without induction (controls, n = 25). Flow cytometry data were correlated to rejection incidence. RESULTS: Compared to controls, CD4(+)CD25(+)FoxP3(+) regulatory T-cell expansion among CD4(+) T cells was noticed in the rATG group at all post-transplant time-points by Day 14 (P < 0.001). A significant decrease in Treg frequency (P < 0.001) and concurrently a transient increase of CD4(+)CD25(low/-)FoxP3(+) population were observed in basiliximab-treated patients 7-60 days post-transplantation. Biopsy-proven acute rejection occurred in 16.7% of controls, 10.7% of the rATG group and in 11.1% of the basiliximab group. Higher CD4(+)FoxP3(+)/CD8(+)CD45RA(+)CD62L(-) ratios were observed repeatedly in those patients after basiliximab induction who were rejection free (P < 0.01). CONCLUSIONS: In this study, the rATG induction therapy was associated with an expansion of regulatory cells. Sustained high CD4(+)FoxP3(+)/Teff ratios were associated with the absence of rejection after basiliximab induction.
Authors: Hans A Schlößer; Uta Drebber; Michael Kloth; Martin Thelen; Sacha I Rothschild; Simon Haase; Maria Garcia-Marquez; Kerstin Wennhold; Felix Berlth; Alexander Urbanski; Hakan Alakus; Astrid Schauss; Alexander Shimabukuro-Vornhagen; Sebastian Theurich; Ute Warnecke-Ebertz; Dirk L Stippel; Alfred Zippelius; Reinhard Büttner; Michael Hallek; Arnulf H Hölscher; Thomas Zander; Stefan P Mönig; Michael von Bergwelt-Baildon Journal: Oncoimmunology Date: 2015-11-09 Impact factor: 8.110
Authors: Marissa M Brokhof; Hans W Sollinger; David R Hager; Brenda L Muth; John D Pirsch; Luis A Fernandez; Janet M Bellingham; Joshua D Mezrich; David P Foley; Anthony M D'Alessandro; Jon S Odorico; Maha A Mohamed; Vijay Vidyasagar; Thomas M Ellis; Dixon B Kaufman; Arjang Djamali Journal: Transplantation Date: 2014-03-27 Impact factor: 4.939
Authors: John R Greenland; Charissa M Wong; Rahul Ahuja; Angelia S Wang; Chiyo Uchida; Jeffrey A Golden; Steven R Hays; Lorriana E Leard; Raja Rajalingam; Jonathan P Singer; Jasleen Kukreja; Paul J Wolters; George H Caughey; Qizhi Tang Journal: Transplantation Date: 2016-10 Impact factor: 4.939
Authors: Kiyohiko Hotta; Akihiro Aoyama; Tetsu Oura; Yohei Yamada; Makoto Tonsho; Kyu Ha Huh; Kento Kawai; David Schoenfeld; James S Allan; Joren C Madsen; Gilles Benichou; Rex-Neal Smith; Robert B Colvin; David H Sachs; A Benedict Cosimi; Tatsuo Kawai Journal: JCI Insight Date: 2016-07-07