title: Impact of Basiliximab on regulatory T-cells early after kidney transplantation: down-regulation of CD25 by receptor modulation.
abstract: Monoclonal anti-CD25-antibodies are successfully applied in organ transplantation to reduce the incidence of acute graft rejection. However, targeting the CD25 molecule might not only affect activated T-cells but also regulatory T-cells (T(regs)) constitutively expressing the CD4(+)CD25(+)CD127(low)FoxP3(+) phenotype. In this study, we investigated the influence of the anti-CD25-antibody Basiliximab on the frequency of T(regs) early after kidney transplantation comparing individuals receiving/not receiving induction therapy (n = 14 and n = 7). Following Basiliximab administration, a distinct loss of CD4(+)CD25(high) T-cells was observed lasting for at least 6 weeks. This was not accompanied by a disappearance of the entire CD4(+)CD25(+)FoxP3(+) T(regs) but rather a decreased expression density of CD25 on the latter. In addition, a transient rise in CD4(+)CD25(-)FoxP3(+) T-cells was found which expressed the CD127(low) phenotype. Thus, a phenotypic shift of T(regs) from the CD25(+) to the CD25(-) compartment was suggested. This was supported by in vitro findings showing that the disappearance of CD4(+)CD25(high) cells in the presence of Basiliximab was due to down-regulation of CD25 expression meanwhile the suppressive function of these cells was maintained. In conclusion, Basiliximab therapy directly affects CD4(+)CD25(+)CD127(low)FoxP3(+) T(regs) but does not seem to be associated with functional consequences. Thus, it is unlikely that Basiliximab treatment negatively influences strategies involving T(regs) to promote tolerance after organ transplantation.
authors: Transplant Laboratory, Department of General, Visceral and Transplantation Surgery, Hannover Medical School, Hannover, Germany.
authors: Florian Wolfgang Rudolf
authors: FW
authors: Vondran
authors: Kai
authors: K
authors: Timrott
authors: Janice
authors: J
authors: Tross
authors: Sonja
authors: S
authors: Kollrich
authors: Anke
authors: A
authors: Schwarz
authors: Frank
authors: F
authors: Lehner
authors: Juergen
authors: J
authors: Klempnauer
authors: Thomas
authors: T
authors: Becker
authors: Reinhard
authors: R
authors: Schwinzer
mesh_terms: D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D000077552:Basiliximab; D001706:Biopsy; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology; D049109:Cell Proliferation; D015536:Down-Regulation; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D053645:Interleukin-2 Receptor alpha Subunit / Q000096:biosynthesis*; D007668:Kidney / Q000378:metabolism*; D016030:Kidney Transplantation / Q000379:methods*; D008297:Male; D008875:Middle Aged; D011993:Recombinant Fusion Proteins / Q000627:therapeutic use*; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000276:immunology*
chemical_list: D000911:Antibodies, Monoclonal; D007166:Immunosuppressive Agents; D053645:Interleukin-2 Receptor alpha Subunit; D011993:Recombinant Fusion Proteins; D000077552:Basiliximab