CD4+CD25+FOXP3+ regulatory t cells increase De novo in kidney transplant patients after immunodepletion with Campath-1H
CD4+CD25+FOXP3+ regulatory t cells increase De novo in kidney transplant patients after immunodepletion with Campath-1H
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DOI：
10.1111/j.1600-6143.2007.02134.x
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发表时间：
2008-04-01
影响因子：
8.8
通讯作者：
Knechtle, S. J.
中科院分区：
文献类型：
--
作者：
Bloom, D. D.;Chang, Z.;Knechtle, S. J.
坎帕斯-1H（阿仑单抗）是一种用于肾移植的有效免疫耗竭剂。为了评估其在免疫细胞重建过程中对T淋巴细胞的影响，我们分析了接受坎帕斯-1H治疗的肾移植受者的外周血中FOXP3（＋）调节性T（Treg）细胞的存在情况。流式细胞术显示，在CD4（＋）T细胞群中，CD4（＋）CD25（＋）FOXP3（＋）淋巴细胞显著增加，使Treg/Teff（T效应细胞）比值在长达数年的时间内发生偏移。相比之下，接受抗CD25（巴利昔单抗）治疗并使用环孢素A维持治疗的患者，其Treg水平持续下降。坎帕斯-1H治疗患者的Tregs增加与维持性免疫抑制无关。重要的是，Tregs的增加不能完全用其稳态增殖、胸腺输出增加或Treg保留来解释，这提示了其新生的产生/扩增。与此一致的是，在体外用坎帕斯-1H（无论是否加用抗CD3）刺激外周血单个核细胞，激活后会导致具有抑制能力的CD4（＋）CD25（＋）FOXP3（＋）细胞增加。总之，这些数据表明坎帕斯-1H促进外周Tregs增加，并可能在体内作为Tregs的内在产生因素。
Campath-1H (Alemtuzumab) is an effective immunodepletion agent used in renal transplantation. To evaluate its influence on T lymphocytes during repletion, we analyzed peripheral blood from Campath-1H-treated renal allograft recipients for the presence of FOXP3(+) regulatory T (Treg) cells. Flow cytometry demonstrated that CD4(+)CD25(+)FOXP3(+) lymphocytes increased significantly within the CD4(+) T-cell population, skewing Treg/Teff (T effector) ratios for up to several years. In contrast, Treg levels in patients treated with anti-CD25 (Basiliximab) and maintained on CsA demonstrated a sustained decrease. The increase in Tregs in Campath-1H treated patients developed independent of maintenance immunosuppression. Importantly, the increase in Tregs was not fully explained by their homeostatic proliferation, increased thymic output, or Treg sparing, suggesting de novo generation/expansion. Consistent with this, in vitro stimulation of PBMCs with Campath-1H, with or without anti-CD3, activation led to an increase in CD4(+)CD25(+)FOXP3(+) cells that had suppressive capabilities. Together, these data suggest that Campath-1H promotes an increase in peripheral Tregs and may act as an intrinsic generator of Tregs in vivo.