摘要
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1 d受者细胞输注组(+1 d group)、移植后4 d受者细胞输注组(+4 d group)、移植后7 d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4 d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7 d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4 d,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。
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.
引文
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