Experimental Extracorporeal Photopheresis Inhibits the Sensitization and Effector Phases of Contact Hypersensitivity via Two Mechanisms: Generation of IL-10 and Induction of Regulatory T Cells
Experimental Extracorporeal Photopheresis Inhibits the Sensitization and Effector Phases of Contact Hypersensitivity via Two Mechanisms: Generation of IL-10 and Induction of Regulatory T Cells
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DOI：
10.4049/jimmunol.181.9.5956
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发表时间：
2008-11-01
影响因子：
4.4
通讯作者：
Schwarz, Thomas
中科院分区：
文献类型：
--
作者：
Maeda, Akira;Schwarz, Agatha;Schwarz, Thomas
体外光采术（ECP）用于治疗免疫介导的疾病，包括移植排斥和移植物抗宿主病。利用接触超敏反应 (CHS) 的 ECP 实验鼠模型表明，ECP 抑制 CHS 致敏并诱导调节性 T 细胞 (Treg)。在本研究中，我们发现ECP不仅抑制CHS的致敏，而且抑制CHS的效应期，而Treg仅抑制致敏。 IL-10 被确定为效应期抑制的关键成分，也是 Treg 发育的驱动力。因此，我们认为 ECP 对 CHS 效应期的抑制是一个不需要 Treg 的过程，但可能通过增强的 IL-10 介导，如使用 IL-10 缺陷小鼠所表明的那样。这表明 ECP 至少有两种作用机制，一种抑制 CHS 的效应器阶段，另一种产生 Treg，而 Treg 反过来又可以抑制 CHS 致敏并负责可转移的保护。总之，这可能有助于解释 ECP 在预防、急性和治疗环境中的临床益处。免疫学杂志，2008 年，181：5956-5962。
Extracorporeal photopheresis (ECP) is used to treat immune-mediated diseases including transplant rejection and graft-vs-host-disease. An experimental murine model of ECP utilizing contact hypersensitivity (CHS) revealed that ECP inhibits the sensitization of CHS and induces regulatory T cells (Treg). In this study, we find that ECP inhibits not only the sensitization but also the effector phase of CHS, although Treg only inhibited sensitization. IL-10 was determined to be a critical component of the effector phase inhibition and also a driving force in developing Treg. Thus, we propose that the inhibition of the effector phase of CHS by ECP is a process that does not require Treg but may be mediated via enhanced IL-10 as suggested by the use of IL-10-deficient mice. This suggests that ECP has at least two mechanisms of action, one inhibiting the effector phase of CHS and one generating Treg, which in turn can inhibit CHS sensitization and is responsible for the transferable protection. Together, this may help explain the clinical benefits of ECP in prophylactic, acute, and therapeutic settings. The Journal of Immunology, 2008, 181:5956-5962.