rhG-CSF对健康供者T细胞CCR5表达的不同调控及其与急性移植物抗宿主病的相关性研究

探讨重组人粒细胞集落刺激因子(rhG-CSF)对健康供者T细胞趋化因子受体CCR5表达的影响及其与急性移植物抗宿主病(aGVHD)的相关性,从而了解rhG-CSF动员在异基因造血干细胞移植(allo-HSCT)后诱导免疫耐受的机制。选取68名亲缘allo-HSCT健康供者及相应的68例受者为研究对象,应用流式细胞技术测定健康供者rhG-CSF动员前后外周血CD4+和/CD8+T细胞表面CCR5的表达,比较其变化。根据动员前后供者外周血CD4+/CD8+T细胞表面CCR5的表达变化情况,将其中可供分析的62例供者分为表达下调组和未下调组,比较两组受者II-IV度aGVHD的累计发生率。结果表明,与动员前外周血相比,rhG-CSF动员后的外周血中CD4+和CD8+T细胞表面CCR5表达均值无明显变化,但在不同个体之间表现出明显的不一致性。34例(50%)供者CD4+细胞CCR5表达下调,50%表达不变或上调,而42例(61.8%)供者CD8+T细胞CCR5表达下调,26例(38.3%)供者CCR5表达不变或上调。分析可供评价的62例移植患者表明,供者CD4+T细胞CCR5下调组受者II-IV度aGVHD发生率较未下调组明显降低(16.6%vs 43.3%,P=0.032),而CD8+T细胞CCR5下调组受者II-IV度aGVHD的累计发生率较未下调组呈现增高趋势(37.8%vs 16.0%,P=0.065)。结论:rhG-CSF动员影响T细胞表面CCR5的表达,而这些作用可能影响T细胞体内迁移行为,减少T细胞向GVHD靶器官聚集,从而降低allo-HSCT后aGVHD的发生率。

Differential Regulation of CCR5 Expression on T lymphocytes in Healthy Donors after Mobilization with rhG-CSF and Its Correlation with aGVHD

This study was to investigate the differential regulation of CCR5 expression on T cells in healthy donors after mobilization with recombinant human granulocyte colony-stimulating factor（rhG-CSF） and analyze its correlation with acute graft-versus-host disease（aGVHD） so as to understand the possible mechanisms underlying rhG-CSF-induced immune tolerance.Sixty-eight related healthy donor and their corresponding recipient for allogeneic hematopoietic stem cell transplantation（allo-HSCT） were enrolled in this study.The expression of CCR5 on CD4＋ and CD8＋ T cells in the peripheral blood（PB） before and after mobilization were detected by using flow cytometry（FCM） respectively.According to the changes of CCR5 expression on CD4＋ and CD8＋ T cells,the Sixty-two evaluable donors were divided into the downregulated and unchanged/upregulated（non-downregulated） groups,and the incidence of grades II to IV aGVHD in two groups were compared.The results showed that the mean value of CCR5 expression on CD4＋ and CD8＋ T cells in PB was not different significantly after mobilization（P0.05）.Apparent inconsistency was showed among different individuals.Thirty-four（50%） donors displayed downregulation of CCR5 expression,while 34（50%） donors manifestated unchanged or upregulated CCR5 expression on CD4＋ T cells.CCR5 expression on CD8＋ T cells was downregulated in 42（61.8%）,unchanged or upregulated in 26（38.3%） donors.The cumulative incidence of grades II to IV aGVHD in the downregulated and non-downregulated groups for CD4＋ T cells were 16.1% and 41.9%（P=0.032）,and recipients with CCR5 downregulation on CD8＋ T cells showed an increased tendency of developing aGVHD（37.8% vs 16.0%,P = 0.065）.In conclusion,rhG-CSF mobilization could lead to differential regulation of CCR5 expression on T cells,w hich might influence the migration of T cells in vivo,decrease T cell trafficking tow ards GVHD target organs,and thus reduce the incidence of aGVHD after transplantation.