Transplant Laboratory, Department of General, Visceral and Transplantation Surgery, Hannover Medical School, Hannover, Germany.
Transpl Int. 2010 May 1;23(5):514-23. doi: 10.1111/j.1432-2277.2009.01013.x. Epub 2009 Nov 30.
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.
单克隆抗 CD25 抗体在器官移植中成功应用，以降低急性移植物排斥反应的发生率。然而，针对 CD25 分子不仅可能影响激活的 T 细胞，而且还可能影响持续表达 CD4(+)CD25(+)CD127(low)FoxP3(+)表型的调节性 T 细胞（Tregs）。在这项研究中，我们研究了抗 CD25 抗体巴利昔单抗对肾移植后早期 Tregs 频率的影响，比较了接受/未接受诱导治疗的个体（n = 14 和 n = 7）。巴利昔单抗给药后，观察到 CD4(+)CD25(high)T 细胞明显丢失，持续至少 6 周。这并没有伴随着整个 CD4(+)CD25(+)FoxP3(+)Tregs 的消失，而是后者 CD25 的表达密度降低。此外，还发现 CD4(+)CD25(-)FoxP3(+)T 细胞一过性升高，表达 CD127(low)表型。因此，提示 Tregs 从 CD25(+)向 CD25(-)区室发生表型转变。这得到了体外研究结果的支持，表明在巴利昔单抗存在的情况下 CD4(+)CD25(high)细胞的消失是由于 CD25 表达的下调，同时这些细胞的抑制功能得以维持。总之，巴利昔单抗治疗直接影响 CD4(+)CD25(+)CD127(low)FoxP3(+)Tregs，但似乎与功能后果无关。因此，巴利昔单抗治疗不太可能对涉及 Tregs 的器官移植后促进耐受的策略产生负面影响。
