The absolute number of regulatory T cells in unmanipulated peripheral blood grafts predicts the occurrence of acute-graft-versus-host disease post haplo-identical hematopoietic stem cell transplantation
The absolute number of regulatory T cells in unmanipulated peripheral blood grafts predicts the occurrence of acute-graft-versus-host disease post haplo-identical hematopoietic stem cell transplantation
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未操作的外周血移植物中调节性T细胞的绝对数量可以预测单倍体相合造血干细胞移植后急性移植物抗宿主病的发生。
DOI：
10.1016/j.leukres.2017.01.011
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发表时间：
2017-05-01
影响因子：
2.7
通讯作者：
Wang, Heng-Xiang
中科院分区：
文献类型：
--
作者：
Ding, Li;Zhu, Heng;Wang, Heng-Xiang
据报道，CD4(+)CD25(+)Foxp3（+）调节性T细胞（Tregs）在抑制急性移植物抗宿主病（aGVHD）中发挥核心作用，但移植物中的Treg含量是否与单倍相同造血干细胞移植（haploo - hsct）后aGVHD的发生相关尚不清楚。本研究观察动员粒细胞集落刺激因子（G-CSF）前后外周血Tregs的变化。此外，还对骨髓移植和PB移植中Tregs的功能进行了分析。为了探讨Tregs对aGVHD的预后价值，我们对61例患者进行了单倍相同移植物中Tregs的分析。此外，还进行了临床变量和细胞亚群的单变量和多变量分析。结果表明，G-CSF处理后CD4(+) T细胞Tregs百分比和每10(6)个总有核细胞Tregs的绝对数量均显著升高。此外，PB移植物中的Tregs对抗原特异性T细胞增殖的抑制作用比BM移植物中的Tregs更强。引人注目的是，在PB移植中接受更多Tregs的患者aGVHD II-IV的累积发病率较低（36%对58%，P=0.046）。此外，在多变量分析中，PB移植物中treg的数量与aGVHD II-IV的发生率降低显著相关（P=0.02）。相比之下，在本研究中，移植物中treg的数量与aGVHD的发生无关。进一步分析表明，移植物中Treg含量不影响单倍造血干细胞移植后Treg重构、感染率或慢性GVHD发生率。此外，在本研究中没有发现移植物细胞类型与生存终点或复发率之间的显著相关性。总之，我们的研究结果表明，在我们的移植环境中，PB移植中大量的treg与单倍造血干细胞移植中aGVHD的风险降低有关。(C) 2017年Elsevier Ltd.出版
CD4(+)CD25(+)Foxp3(+) regulatory T cells (Tregs) have been reported to play a central role in suppressing acute graft-versus-host disease (aGVHD), but whether the Treg contents of grafts correlates with the occurrence of aGVHD post haplo-identical hematopoietic stem cell transplantation (haplo-HSCT) remains unclear. In the present study, changes in Tregs in peripheral blood (PB) were followed before and after granulocyte colony-stimulating factor (G-CSF) mobilization. In addition, functional analyses of Tregs in PB grafts and bone marrow (BM) grafts were performed. To probe the prognostic value of Tregs for aGVHD, an analysis of Tregs in haplo-identical grafts was conducted in 61 patients. Moreover, univariate and multivariate analyses of both clinical variables and cellular subsets were performed. The results showed that both the percentage Tregs of CD4(+) T cells and absolute numbers of Tregs per 10(6) total nucleated cells significantly increased after G-CSF administration. Additionally, Tregs in PB grafts exhibited a stronger inhibitory effect on antigen-specific T cell proliferation than did Tregs in BM grafts. Strikingly, patients receiving more Tregs in PB grafts had a lower cumulative incidence of aGVHD II-IV (36% versus 58%, P=0.046). Further, in a multivariate analysis, the number of Tregs in PB grafts was significantly associated with a lower occurrence of aGVHD II-IV (P=0.02). In contrast, the number of Tregs in BM grafts was not associated with the occurrence of aGVHD in the current study. Further analysis showed that the Treg content in grafts did not affect Treg reconstitution, infection rate, or incidence of chronic GVHD after haplo-HSCT. Moreover, no significant correlations between cell types in grafts and the survival end points or relapse rates were found in the present study. In conclusion, our results suggest that a high number of Tregs in PB grafts is associated with reduced risk of aGVHD in haplo-HSCT in our transplant settting. (C) 2017 Published by Elsevier Ltd.