High proportions of regulatory T cells in PBSC grafts predict improved survival after allogeneic haematopoietic SCT
High proportions of regulatory T cells in PBSC grafts predict improved survival after allogeneic haematopoietic SCT
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DOI：
10.1038/bmt.2015.215
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发表时间：
2016-01-01
影响因子：
4.8
通讯作者：
Roberts, D. J.
中科院分区：
文献类型：
--
作者：
Danby, R. D.;Zhang, W.;Roberts, D. J.
调节性T细胞（Tregs）在小鼠移植模型中调节免疫应答并提高存活率。然而，异体细胞移植物中的Treg含量是否影响人类造血干细胞（HSC）移植的结果尚未明确。在一项对94例成人异基因外周血干细胞移植（60%为非亲缘供者；85%为减低强度预处理）的前瞻性研究中，移植的Treg（CD3(+)CD4(+)CD25(+)FOXP3(+)CD127(dim/ - )）中位剂量为4.7×10⁶/kg，Tregs占CD4(+) T细胞的中位比例为2.96%。接受Treg/CD4(+) T细胞比值高于中位数的移植物的患者，3年总生存率为75%，而接受Treg/CD4(+) T细胞比值低于中位数的移植物的患者为49%（P = 0.02），3年非复发死亡率分别为13%和35%（P = 0.02）。在多变量分析中，移植物中高Treg/CD4(+) T细胞比值是较低非复发死亡率（风险比（HR），0.30；P = 0.02）、提高总生存率（HR，0.45；P = 0.03）以及提高持续中性粒细胞水平（HR，0.52；P = 0.002）、血小板水平（HR，0.51；P未完整）的独立预测因子。
Regulatory T cells (Tregs) modulate immune responses and improve survival in murine transplant models. However, whether the Treg content of allogeneic cell grafts influences the outcome in human haematopoietic stem cell (HSC) transplantation is not well established. In a prospective study of 94 adult allogeneic PBSC transplants (60% unrelated; 85% reduced intensity conditioning), the median Treg (CD3(+)CD4(+)CD25(+)FOXP3(+)CD127(dim/-)) dose transplanted was 4.7 x 10(6)/kg, with Tregs accounting for a median of 2.96% of CD4(+) T cells. Patients transplanted with grafts containing a Treg/CD4(+) T-cell ratio above the median had a 3-year overall survival of 75%, compared with 49% in those receiving grafts with a Treg/CD4(+) T-cell ratio below the median (P=0.02), with a 3-year non-relapse mortality of 13% and 35%, respectively (P=0.02). In multivariate analysis, a high graft Treg/CD4(+) T-cell ratio was an independent predictor of lower non-relapse mortality (hazard ratio (HR), 0.30; P=0.02), improved overall survival (HR, 0.45; P=0.03) and improved sustained neutrophil (HR, 0.52; P=0.002), platelet (HR, 0.51; P