Extracorporeal photopheresis (ECP) represents one of the most widespread and effective cell therapies for graft‐versus‐host disease and other T cell‐mediated disorders. However, the key factors affecting the therapeutic efficacy of ECP remain unclear. We hypothesized that therapeutic effects are mediated by ECP‐treated antigen‐presenting dendritic cells (DC). To test this hypothesis, we used the experimental model of contact hypersensitivity (CHS). The ECP’s therapeutic activity improved when the total cell dose of the ECP‐treated cells was increased. We used different haptens during sensitization to demonstrate that the anti‐inflammatory activity of ECP is antigen‐specific. This confirmed the hypothesis that professional antigen‐presenting cells are involved in the mode of action. Also, the ECP’s therapeutic activity was abrogated by the depletion of CD11c⁺ DC, which represents fewer than 1% of all the ECP‐exposed cells. Finally, we confirm the critical importance of CD11c⁺ DC for ECP activity by showing that only a few purified CD11c⁺ DC are sufficient to mediate its therapeutic effect. The finding that ECP‐treated, physiological antigen‐presenting DC alone mediate antigen‐specific modulation of a pathological immune response may result in better‐targeted interventions when treating patients.

中文翻译：

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CD11c+树突状细胞介导体外光分离术中的抗原特异性抑制

体外光照（ECP）代表接枝最普遍和有效的细胞疗法之一与宿主疾病和其他 T 细胞介导的疾病。然而，影响ECP治疗效果的关键因素尚不清楚。我们假设治疗效果是由 ECP 处理的抗原呈递树突细胞 (DC) 介导的。为了验证这一假设，我们使用了接触性过敏症 (CHS) 的实验模型。当 ECP 处理细胞的总细胞剂量增加时，ECP 的治疗活性提高。我们在致敏过程中使用了不同的半抗原来证明 ECP 的抗炎活性是抗原特异性的。这证实了专业抗原呈递细胞参与作用模式的假设。此外，ECP 的治疗活性被 CD11c ⁺的消耗所废除DC，占所有 ECP 暴露细胞的不到 1%。最后，我们通过证明只有少数纯化的 CD11c ⁺ DC 足以介导其治疗效果，从而证实了 CD11c ⁺ DC 对 ECP 活性的关键重要性。ECP 治疗的、生理性抗原呈递 DC 单独介导病理免疫反应的抗原特异性调节的发现可能会在治疗患者时产生更好的靶向干预。