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首页> 外文期刊>Cellular immunology >Ex vivo expansion of regulatory T cells from long-term Belatacept-treated kidney transplant patients restores their phenotype and suppressive function but not their FOXP3 TSDR demethylation status
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Ex vivo expansion of regulatory T cells from long-term Belatacept-treated kidney transplant patients restores their phenotype and suppressive function but not their FOXP3 TSDR demethylation status

机译:来自长期脑皮治疗的肾移植患者的监管T细胞的前体内扩张恢复其表型和抑制功能,但不是它们的Foxp3 TSDR去甲基化状态

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We recently reported that Tregs from long-term Belatacept-treated kidney transplant patients displayed an altered phenotype and impaired suppressive function compared to Tregs from healthy controls. However, it remains unknown whether ex vivo expansion of Tregs from patients who underwent long-term immunosuppression may be feasible to be used in their treatment. In this work, Tregs from Belatacept-treated patients were polyclonally expanded in vitro in the presence of rapamycin and IL-2. After four weeks of expansion, Tregs from patients expressed high levels of FOXP3, CD25, CTLA-4, Helios and CCR7, and showed strong suppressive activity, even in the presence of pro-inflammatory cytokines. However, FOXP3 TSDR demethylation remained lower in expanded Tregs from Belatacept-treated patients compared to healthy control Tregs. These data suggest that ex vivo expansion of Tregs from patients undergoing long-term immunosuppression may require the use of epigenetic modifying agents to stabilize FOXP3 expression to be considered as treatment in kidney transplant patients.
机译:我们最近报道,与来自健康对照的Tregs相比,长期乳化治疗的肾移植患者的Tregs显示出改变的表型和抑制功能受损的抑制功能。然而,它仍然未知是否从经过长期免疫抑制的患者中脱脂的exvivo扩张是可行的,以便在治疗中使用。在这项工作中,从雷帕霉素和IL-2存在下,来自脑梗遇治疗的患者的Tregs在体外聚集在体外。在四周的膨胀后,来自患者的Tregs表达了高水平的Foxp3,CD25,CTLA-4,Helios和CCR7,并且即使在促炎细胞因子存在下也表现出强烈的抑制活性。然而,与健康的对照Tregs相比,来自BelataCept治疗的患者的膨胀后,FoxP3 TSDR去甲基化仍然较低。这些数据表明,来自经历长期免疫抑制的患者的Tregs的前体内扩张可能需要使用表观遗传改性剂来稳定Foxp3表达被认为是肾移植患者的治疗。

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