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Monocytes show immunoregulatory capacity on CD4+ T cells in a human in‐vitro model of extracorporeal photopheresis

机译:单核细胞在体外体外血液分离的人类体外模型中显示CD4 + T细胞的免疫调节能力

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摘要

Extracorporeal photopheresis (ECP) is a widely used immunomodulatory therapy for the treatment of various T cell‐mediated disorders such as cutaneous T cell lymphoma (CTCL), graft‐ ‐host disease (GvHD) or systemic sclerosis. Although clinical benefits of ECP are already well described, the underlying mechanism of action of ECP is not yet fully understood. Knowledge on the fate of CD14 monocytes in the context of ECP is particularly limited and controversial. Here, we investigated the immunoregulatory function of ECP treated monocytes on T cells in an ECP model. We show that ECP‐treated monocytes significantly induce proinflammatory T cell types in co‐cultured T cells, while anti‐inflammatory T cells remain unaffected. Furthermore, we found significantly reduced proliferation rates of T cells after co‐culture with ECP‐treated monocytes. Both changes in interleukin secretion and proliferation were dependent on cell‐contact between monocytes and T cells. Interestingly, blocking interactions of programmed death ligand 1 (PD‐L1) to programmed death 1 (PD‐1) in the model led to a significant recovery of T cell proliferation. These results set the base for further studies on the mechanism of ECP, especially the regulatory role of ECP‐treated monocytes.
机译:体外光胆疗法(ECP)是一种广泛使用的免疫调节疗法,用于治疗各种T细胞介导的疾病,例如皮肤T细胞淋巴瘤(CTCL),移植物宿主病(GvHD)或系统性硬化症。尽管已经很好地描述了ECP的临床益处,但是尚未完全理解ECP的潜在作用机理。关于ECP背景下CD14单核细胞的命运的知识特别有限且存在争议。在这里,我们研究了ECP模型中经ECP处理的单核细胞对T细胞的免疫调节功能。我们显示,经ECP处理的单核细胞可在共培养T细胞中显着诱导促炎性T细胞类型,而抗炎性T细胞仍不受影响。此外,我们发现与ECP处理的单核细胞共培养后,T细胞的增殖速率显着降低。白细胞介素分泌和增殖的变化均取决于单核细胞和T细胞之间的细胞接触。有趣的是,在模型中阻断程序性死亡配体1(PD-L1)与程序性死亡1(PD-1)的相互作用导致T细胞增殖的显着恢复。这些结果为进一步研究ECP的机制,尤其是ECP处理的单核细胞的调节作用奠定了基础。

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