Regulatory T Cells and Extracorporeal Photochemotherapy: Correlation With Clinical Response and Decreased Frequency of Proinflammatory T Cells
Regulatory T Cells and Extracorporeal Photochemotherapy: Correlation With Clinical Response and Decreased Frequency of Proinflammatory T Cells
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DOI：
10.1097/tp.0b013e3181a27a5d
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发表时间：
2009-05-15
期刊：
影响因子：
6.2
通讯作者：
Biagi, Ettore
中科院分区：
文献类型：
--
作者：
Di Biaso, Iolanda;Di Maio, Lucia;Biagi, Ettore
背景体外光化学疗法（ECP）治疗难治性/耐药性移植物抗宿主病（GvHD）的免疫机制是复杂的。我们先前分析了CD 4（+）CD 25（+）Foxp 3（+）调节性T细胞（T-T细胞）的作用。在当前的研究中，我们扩大了人群规模（n=27;慢性GvHD=18，急性GvHD=9），中位随访时间为24个月。监测T细胞的CD 4、CD 25、糖皮质激素诱导的肿瘤坏死因子受体（GITR）、CD 62 L、CCR 7、Foxp 3和STAT-5。用IL-17 Elispot对分泌IL-17的循环辅助性T细胞CD 4（+）进行免疫分析，IL-17是被认为与GvHD发病机制相关的T细胞亚群。我们证实ECP伴随着CD 4（+）CD 25（+）Foxp 3（+）GITR（+）CD 62 L（+）CCR 7（+）T细胞的显著增加。分选的T-STAT显示STAT-5的磷酸化增强。只有ECP应答的患者表现出循环T-CRP的升高，主要受慢性GvHD的影响。此外，这种现象对应于IL-17的分泌减少。总之，我们的研究表明，T-CRP代表ECP在受GvHD影响的患者中的临床益处的重要免疫介质。
Background. Immune mechanisms of extracorporeal photochernotherapy (ECP) in refractory/resistant graft-versus-host disease (GvHD) are complex. We have previously analyzed the role of CD4(+)CD25(+)Foxp3(+) regulatory T cells (T-regs).Methods. In the current study, we have enlarged the size of the population (n=27; chronic GvHD=18, acute GvHD=9) for a median follow-up of 24 months. T-regs were monitored for CD4, CD25, glucocorticoid-induced tumor necrosis factor receptor (GITR), CD62L, CCR7, Foxp3, and STAT-5. Immune analysis by interleukin (IL)-17 Elispot was carried out on circulating T-helper CD4(+) cells secreting IL-17, a subset of T cells considered relevant in the pathogenesis of GvHD.Results. We confirm that ECP is accompanied by a significant increase of CD4(+)CD25(+)Foxp3(+)GITR(+)CD62L(+)CCR7(+) T-regs. Sorted T-regs show augmented phosphorylation of STAT-5. Only ECP-responding patients demonstrate a raise of circulating T-regs, being mostly affected by chronic GvHD. Moreover, this phenomenon corresponds to a diminished secretion of IL-17.Discussion. In conclusion, our study shows that T-regs represent important immune mediators of the clinical benefits of ECP in patients affected by GvHD.