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.

中文翻译：

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长期接受Belatacept治疗的肾移植患者体内调节性T细胞的离体扩增可恢复其表型和抑制功能，但不能恢复其FOXP3 TSDR去甲基化状态。

我们最近报道，与健康对照组的Treg相比，长期接受Belatacept治疗的肾脏移植患者的Treg表现出改变的表型和抑制功能受损。然而，从接受长期免疫抑制的患者体内分离Tregs是否可用于治疗尚不明确。在这项工作中，在雷帕霉素和IL-2的存在下，来自Belatacept治疗患者的Treg在体外进行多克隆扩增。扩增四周后，即使存在促炎性细胞因子，来自患者的Treg仍表达高水平的FOXP3，CD25，CTLA-4，Helios和CCR7，并表现出强大的抑制活性。但是，与健康对照Treg相比，来自Belatacept治疗的患者的扩增Treg中的FOXP3 TSDR去甲基化仍然较低。