不同时间输注受者动员脾细胞对小鼠单倍体相合造血干细胞移植后移植物抗宿主病的影响

摘要

Objective:To explore the effect of infusing G-CSF mobilized recipient spleen cells at different time after haploidentical stem cell transplantation (HSCT) on graft-versus-host disease (GVHD) in mice and its possible mechanism.Methods:Forty mice after HSCT were randomly divided into 4 groups (n =10):GVHD positive control group (control group),1st d recipient cell infusion group after transplantation (+ 1 d group),4th d recipient cell infusion group after transplantation(+ 4 d group),7th d recipient cell infusion group after transplantation (+ 7 d group).The mice in control group were injected the normal saline of same equivalent with experimental group which were given the same amount of G-CSF-mobilized recipient spleen cells.The general manifestation and pathological change of GVHD were observed.The expression changes of CD3 + CD4 +,CD3 + CD8 + cell subsets and FasL in peripheral blood were detected by flow cytometry.Results:The incidence of GVHD was significantly decreased in + 4 d group and the median survival time was longer than 60 days,which was significantly higher than that of control group (24 d),+ 1 d group (21 d),+ 7 d group (28 d).(P ＜ 0.01,P ＜ 0.01,P ＜ 0.01).The Fasl expression of peripheral blood T lymphocytes in + 4 d group were significantly lower than that in the other 3 groups (P ＜ 0.05).Conclusion:The + 4 d infusion of G-CSF mobilized recipient spleen cells on 4th day after haploidentical HSC transplantation can inhibit the expression of FasL in donor T lymphocytes,and significantly reduce the incidence of GVHD.%目的:研究小鼠单倍体相合造血干细胞移植后不同时间输注G-CSF动员的自体脾细胞对移植物抗宿主病(GVHD)的影响,并初步探讨其可能机制.方法:将40只造血干细胞移植后的小鼠随机分为4组(n=10):GVHD阳性对照组(control group)、移植后1d受者细胞输注组(+1 d group)、移植后4d受者细胞输注组(+4 dgroup)、移植后7d受者细胞输注组(+7 d group).输注3×10 7的G-CSF动员后的受者脾细胞,观察GVHD临床体征及病理变化,并检测各组外周血中CD3+ CD4+、CD3+CD8+细胞亚群及其FasL的表达变化.结果:移植后4d组的GVHD发生率明显降低,中位存活时间＞60 d,显著高于对照(24 d)、移植后1 d(21 d)和移植后7d组(28 d)(P＜0.01),而外周血中T淋巴细胞Fasl的表达显著低于其他3组(P＜0.05).结论:单倍体相合的造血干细胞移植后4d,输注G-CSF动员的受者脾细胞能抑制供者T淋巴细胞的FasL的表达,显著减少GVHD的发生.