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Impact of Basiliximab on regulatory T‐cells early after kidney transplantation: down‐regulation of CD25 by receptor modulation
Authors:Florian Wolfgang Rudolf Vondran  Kai Timrott  Janice Tross  Sonja Kollrich  Anke Schwarz  Frank Lehner  Juergen Klempnauer  Thomas Becker  Reinhard Schwinzer
Affiliation:1. Transplant Laboratory, Department of General, Visceral and Transplantation Surgery, Hannover Medical School, Hannover, Germany;2. Department of Nephrology, Hannover Medical School, Hannover, Germany
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 (Tregs) constitutively expressing the CD4+CD25+CD127lowFoxP3+ phenotype. In this study, we investigated the influence of the anti‐CD25‐antibody Basiliximab on the frequency of Tregs early after kidney transplantation comparing individuals receiving/not receiving induction therapy (n = 14 and n = 7). Following Basiliximab administration, a distinct loss of CD4+CD25high T‐cells was observed lasting for at least 6 weeks. This was not accompanied by a disappearance of the entire CD4+CD25+FoxP3+ Tregs 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 CD127low phenotype. Thus, a phenotypic shift of Tregs from the CD25+ to the CD25? compartment was suggested. This was supported by in vitro findings showing that the disappearance of CD4+CD25high 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+CD127lowFoxP3+ Tregs but does not seem to be associated with functional consequences. Thus, it is unlikely that Basiliximab treatment negatively influences strategies involving Tregs to promote tolerance after organ transplantation.
Keywords:anti‐IL‐2R  basiliximab  down‐regulation  modulation  regulatory T‐cells  transplantation
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