异基因造血干细胞移植后动态监测调节性T淋巴细胞的临床意义

The clinical significance of dynamic changes of CD4^+ CD25^+ regulatory T cells in patients subject to allogeneic hematopoietic stem cell transplantation

目的探讨监测调节性T淋巴细胞(Treg)的动态变化在异基因造血干细胞移植(allo- HSCT)中的临床意义。方法选择45例allo-HSCT患者,其中31例采用短程甲氨蝶呤(MTX)联合环孢紊A(CsA)预防移植物抗宿主病(GVHD),另14例加用霉酚酸酯(MMF)和达利珠单抗(抗CD25单克隆抗体)强化GVHD的预防。采用流式细胞术动态监测allo-HSCT患者移植预处理前、移植后2、4、8、12周时及发生急性移植物抗宿主病(aGVHD)时外周血Treg的水平;分析Treg水平的变化与aGVHD发生的相互关系。结果45例患者中,发生Ⅱ～Ⅳ度aGVHD10例。移植后8和12周时,未使用达利珠单抗组中发生Ⅱ～Ⅳ度aGVHD较发生0～Ⅰ度aGVHD的患者外周血Treg水平显著降低,差异有统计学意义(P<0.05);患者发生Ⅱ～Ⅳ度aGVHD后,外周血Treg水平较发生前显著降低。差异有统计学意义(P<0.05)。使用达利珠单抗组的患者外周血Treg水平在各时间点均明显降低,各时点间比较,差异均无统计学意义。结论Treg的动态变化与aGVHD的关系密切,可作为临床监测aGVHD发生的重要指标之一;达利珠单抗的应用显著降低了外周血Treg的水平,其对aGVHD的预防作用有待今后深入研究。

Objective To investigate the clinical significance of dynamic changes of CD4^＋ CD25^＋ regulatory T cells （Treg） in patients subject to allogeneic hematopoietic stem cell transplantation （allo-HSCT）. Methods Forty-five patients received allo-HSCT. The graft-vesus-host disease （GVHD） was prevented by cyclosporine A and short-term MTX regimen in 31 patients. Fourteen of all the patients received Zenapox （CD25MAb） at the day of transplantation and day 4 after transplanation. The levels of Treg in peripheral blood were detected by flow cytometry from 45 patients at 2nd, 4th, 8th and 12th week after allo-HSCT and the time of aGVHD development, respectively. Results Anti-CD25 could suppress the peripheral blood levels of Treg significantly. The Treg levels were significantly higher in patients with grade 0-1 aGVHD than those with 2-4 aGVHD at 8th and 12th week after transplantation. Among patients with 2-4 aGVHD, Treg levels were significantly low- er after development of aGVHD than before. Conclusions Treg are important for the aGVHD prevention and can be a useful clinical surveillant index for the development of aGVHD. It can significantly decrease the levels of Treg in the peripheral blood with anti-CD25.