TGF-β-induced CD4+Foxp3+ T cells attenuate acute graft-versus-host disease by suppressing expansion and killing of effector CD8+ cells.

TGF-β-induced CD4+Foxp3+ T cells attenuate acute graft-versus-host disease by suppressing expansion and killing of effector CD8+ cells.
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DOI:
10.4049/jimmunol.1400207
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发表时间:
2014-10-01
期刊:
Journal of immunology (Baltimore, Md. : 1950)
影响因子:
--
通讯作者:
Zheng SG
Zheng SG
中科院分区:
其他
文献类型:
--
作者:
Gu J;Lu L;Chen M;Xu L;Lan Q;Li Q;Liu Z;Chen G;Wang P;Wang X;Brand D;Olsen N;Zheng SG

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TGF-β 诱导的 CD4+Foxp3+ T 细胞 (iTreg) 已被确定为自身免疫性疾病和其他疾病细胞治疗的重要预防和治疗策略。然而,iTregs 作为急性移植物抗宿主病 (GVHD) 治疗方式的潜在用途尚未实现,因为 iTregs 在这种疾病中可能不稳定且抑制性较差。在这里,我们在两种不同的小鼠模型中重新研究了 iTreg 预防和治疗急性 GVHD 的能力。我们的结果表明,只要使用适当的 iTreg 生成方案,这些 iTreg 始终表现出控制急性 GVHD 发展并降低急性 GVHD 动物模型死亡率的强大能力。 iTreg 输注显着抑制供体 CD8+ 细胞和 CD4+ 细胞的植入、颗粒酶 A 和 B 的表达、供体 CD8+ 细胞的细胞毒性作用以及急性 GVHD 中 T 细胞细胞因子的产生。因此,我们得出的结论是,只要采用正确的方法来生成 iTreg 细胞,iTreg 确实可以预防甚至治疗急性 GVHD。
TGF-β-induced CD4+Foxp3+ T cells (iTregs) have been identified as important prevention and treatment strategies for cell therapy in autoimmune diseases and other disorders. However, the potential use of iTregs as a treatment modality for acute graft-verse-host disease (GVHD) has not been realized because iTregs may be unstable and less suppressive in this disease. Here we restudied the ability of iTregs to prevent and treat acute GVHD in two different mouse models. Our results showed that so long as an appropriate iTreg-generation protocol is used, these iTregs consistently displayed a potent ability to control acute GVHD development and reduce mortality in the acute GVHD animal models. iTreg infusion markedly suppressed the engraftment of donor CD8+ cells and CD4+ cells, the expression of Granzyme A and B, the cytotoxic effect of donor CD8+ cells and the production of T cell cytokines in acute GVHD. We therefore conclude that so long as the right methods for generating iTreg cells have been employed, iTregs can indeed prevent and even treat acute GVHD.
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