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Short-term anti-CD25 monoclonal antibody administration down-regulated CD25 expression without eliminating the neogenetic functional regulatory T cells in kidney transplantation

机译:短期抗CD25单克隆抗体给药在肾脏移植中下调CD25表达而不消除新功能调节性T细胞

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摘要

CD4+CD25+ forkhead box P3 (FoxP3)+regulatory T (Treg) cells are generated and play a key role in the induction and maintenance of transplant tolerance in organ recipients. It has been proposed that interleukin (IL)-2/IL-2 receptor (IL-2R) signalling was essential for the development and proliferation of antigen-activated T cells that included both effector T cells and Treg cells. Basiliximab (Simulect™), a chimeric monoclonal antibody directed against the α-chain of the IL-2R (CD25), can be expected to not only affect alloreactive effector T cells, but also reduce the number and function of Treg cells. We therefore examined the effect of basiliximab induction therapy on the number and function of the Treg cells in renal recipients. Basiliximab decreased the percentage of CD4+CD25+T cells, but failed to influence the percentage of CD4+FoxP3+ Treg cells. The cellular CD25 expression was decreased significantly by basiliximab injection, but CD4+CD25+ T cells was not depleted from the circulating pool through monoclonal antibody activation-associated apoptosis. Functional analysis revealed that inhibitory function of Treg cells from recipients with basiliximab injection was not significantly different from recipients without injection. These data indicate that the functional Treg population may not be influenced by short-term basiliximab treatment.
机译:CD4 + CD25 +叉头盒P3(FoxP3)+调节性T(Treg)细胞产生,并在诱导和维持器官接受者的移植耐受性中起关键作用。已经提出白介素(IL)-2 / IL-2受体(IL-2R)信号转导对于包括效应T细胞和Treg细胞的抗原激活T细胞的发育和增殖是必不可少的。 Basiliximab(Simulect™)是针对IL-2R(CD25)的α链的嵌合单克隆抗体,可以预期不仅会影响同种异体效应T细胞,而且会减少Treg细胞的数量和功能。因此,我们检查了巴利昔单抗诱导疗法对肾受体中Treg细胞数量和功能的影响。 Basiliximab降低了CD4 + CD25 + T细胞的百分比,但未能影响CD4 + FoxP3 + Treg细胞的百分比。巴利昔单抗注射后细胞CD25表达显着降低,但CD4 + CD25 + T细胞并未通过单克隆抗体激活相关的凋亡而从循环池中耗竭。功能分析表明,接受巴利昔单抗注射的受试者的Treg细胞的抑制功能与未注射受体的受试者的Treg细胞的抑制作用没有显着差异。这些数据表明功能性Treg人群可能不受短期巴利昔单抗治疗的影响。

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