Liu Jiangying, Xu Lan-Ping, Bian Zhilei, Chang Ying-Jun, Wang Yu, Zhang Xiao-Hui, Huang Xiao-Jun
Peking University People's Hospital, Peking University Institute of Hematology, Beijing Key laboratory of Hematopoietic Stem Cell Transplantation, 11 Xizhimen South Street, Beijing, 100044, China.
J Transl Med. 2015 Dec 30;13:391. doi: 10.1186/s12967-015-0748-x.
In vivo depletion of host T cells with antithymocyte globulin (ATG) is a common strategy for preventing graft-versus-host disease in allogeneic hematopoietic stem cell transplantation (HSCT). The total dose of ATG in conditioning regimens appears to be an important factor that influences the outcome in recipients of transplants. However, the optimal ATG dosage has not been established to date. It remains unclear whether, in the setting of haploidentical HSCT (haploHSCT), different doses of ATG might exert differential influences on the recovery of lymphocyte subpopulations.
This retrospective study analyzed lymphocyte recovery and its correlation to viral infection in two groups of patients that received different doses of ATG before haploHSCT. We performed flowcytometry to determine immunophenotypes of CD19(+) B cells and CD3(+), CD4(+), CD8(+), CD4(+)CD45RA(+), CD4(+)CD45RO(+), CD4(+)CD28(+), CD8(+)CD28(+), and CD4(-)CD8(-) T cells.
We found that, compared to 6 mg/kg, 10 mg/kg ATG significantly hampered the recoveries of CD4(+), CD4(+)CD45RA(+), and CD4(+)CD45RO(+) T cells in the first 2 months following haploHSCT. Similarly, compared to 6 mg/kg, the 10 mg/kg dose of ATG negatively influenced the recoveries of CD4(-)CD8(-) and CD8(+)CD28(+) T cells; recovery was delayed for 6 and 12 months after transplantation, respectively. Moreover, we showed that an increase in Epstein-Barr virus (EBV) infections, associated with the higher dose of ATG, was correlated with the delayed recovery of CD4(-)CD8(-) double negative T cells.
The present study revealed a differential impact of different ATG conditioning doses on the recoveries of T cell subpopulations post-haploHSCT. This study was the first to connect the recovery of CD4(-)CD8(-) T cells to the risk of EBV infection after HSCT. These findings will facilitate optimization of the ATG conditioning dosage and improve the outcome of patients with leukemia that receive haploHSCT.
使用抗胸腺细胞球蛋白（ATG）在体内清除宿主T细胞是异基因造血干细胞移植（HSCT）中预防移植物抗宿主病的常用策略。预处理方案中ATG的总剂量似乎是影响移植受者预后的一个重要因素。然而，迄今为止尚未确定最佳的ATG剂量。在单倍体相合HSCT（haploHSCT）情况下，不同剂量的ATG是否会对淋巴细胞亚群的恢复产生不同影响仍不清楚。
这项回顾性研究分析了两组在haploHSCT前接受不同剂量ATG的患者的淋巴细胞恢复情况及其与病毒感染的相关性。我们进行了流式细胞术以确定CD19(+) B细胞以及CD3(+)、CD4(+)、CD8(+)、CD4(+)CD45RA(+)、CD4(+)CD45RO(+)、CD4(+)CD28(+)、CD8(+)CD28(+)和CD4(-)CD8(-) T细胞的免疫表型。
我们发现，与6 mg/kg相比，10 mg/kg ATG在haploHSCT后的前2个月显著阻碍了CD4(+)、CD4(+)CD45RA(+)和CD4(+)CD45RO(+) T细胞的恢复。同样，与6 mg/kg相比，10 mg/kg剂量的ATG对CD4(-)CD8(-)和CD8(+)CD28(+) T细胞的恢复产生负面影响；移植后恢复分别延迟了6个月和12个月。此外，我们表明，与较高剂量ATG相关的爱泼斯坦 - 巴尔病毒（EBV）感染增加与CD4(-)CD8(-)双阴性T细胞的恢复延迟相关。
本研究揭示了不同ATG预处理剂量对haploHSCT后T细胞亚群恢复的不同影响。这项研究首次将CD4(-)CD8(-) T细胞的恢复与HSCT后EBV感染风险联系起来。这些发现将有助于优化ATG预处理剂量，并改善接受haploHSCT的白血病患者的预后。
