Extracorporeal photochemotherapy (ECP) that takes advantage of the immunomodulatory effects of UV light has been extensively used for many years for the treatment of several T cell-mediated diseases, including graft-versus-host disease (GvHD) and systemic scleroderma. Immune mechanisms that lead to the establishment of T cell tolerance in ECP-treated patients remain poorly known. In this study, we have tested the effect of UV/psoralen-treated BM-derived dendritic cells, referred to as ECP-BMDCs on the outcome of an antigen-specific T cell-mediated reaction, that is, contact hypersensitivity (CHS), which is mediated by CD8+ effector T cells (CD8+ Teff ). The intravenous (i.v.) injection of antigen-pulsed ECP-BMDCs in recipient C57BL/6 mice induced specific CD8+ T cells endowed with immunomodulatory properties (referred to as CD8+ TECP ), which prevented the priming of CD8+ Teff and the development of CHS, independently of conventional CD4+ regulatory T cells. CD8+ TECP mediated tolerance by inhibiting the migration and functions of skin DC and subsequently the priming of CD8+ Teff . CD8+ TECP displayed none of the phenotypes of the usual CD8+ T regulatory cells described so far. Our results reveal an underestimated participation of CD8+ T cells to ECP-induced immunomodulation that could explain the therapeutic effects of ECP in T cell-mediated diseases.

中文翻译：

---

CD8 + T细胞在体外光化学疗法的模型中介导紫外线A诱导的免疫调节。

利用紫外线的免疫调节作用的体外光化学疗法（ECP）已广泛用于治疗多种T细胞介导的疾病，包括移植物抗宿主病（GvHD）和全身性硬皮病。导致在ECP治疗的患者中建立T细胞耐受性的免疫机制仍知之甚少。在这项研究中，我们测试了经紫外线/补骨脂素处理的BM衍生的树突状细胞，即ECP-BMDC，对抗原特异性T细胞介导的反应（即接触性超敏反应（CHS））的结果的影响，它是由CD8 +效应T细胞（CD8 + Teff）介导的。在受体C57BL / 6小鼠中静脉内（iv）注射抗原脉冲的ECP-BMDC诱导了具有免疫调节特性的特异性CD8 + T细胞（称为CD8 + TECP），与传统的CD4 +调节性T细胞无关，它阻止了CD8 + Teff的引发和CHS的发展。CD8 + TECP通过抑制皮肤DC的迁移和功能以及随后引发CD8 + Teff介导了耐受性。CD8 + TECP迄今未显示任何普通CD8 + T调节细胞的表型。我们的结果表明，CD8 + T细胞对ECP诱导的免疫调节的参与被低估了，这可能解释了ECP在T细胞介导的疾病中的治疗作用。CD8 + TECP迄今未显示任何普通CD8 + T调节细胞的表型。我们的结果表明，CD8 + T细胞对ECP诱导的免疫调节的参与被低估了，这可能解释了ECP在T细胞介导的疾病中的治疗作用。CD8 + TECP迄今未显示任何普通CD8 + T调节细胞的表型。我们的结果表明，CD8 + T细胞对ECP诱导的免疫调节的参与被低估了，这可能解释了ECP在T细胞介导的疾病中的治疗作用。