Impact of Basiliximab on regulatory T-cells early after kidney transplantation: down-regulation of CD25 by receptor modulation

P>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+CD127lowFoxP3+ 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+CD25high 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 CD127low 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+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+ 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.