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

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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。 To investigate the effect of recombinant human granulocyte-colony stimulating factor (rhG-CSF) on the expression of chemokine receptor CCR5 in healthy donors and its relationship with acute graft-versus-host disease (aGVHD) Mechanisms to induce immune tolerance after allo-HSCT. Sixty-eight allo-HSCT healthy donors and 68 corresponding recipients were enrolled in this study. Flow cytometry was used to determine the expression of CCR5 on the surface of CD4 + and / CD8 + T lymphocytes in peripheral blood of healthy donors before and after rhG-CSF mobilization Its change. According to the changes of the expression of CCR5 on the surface of CD4 + / CD8 + T cells in the peripheral blood of the donor before and after mobilization, 62 donors for analysis were divided into the down-regulated group and the non-down-regulated group, and the II-IV degree aGVHD The cumulative incidence. The results showed that compared with the pre-mobilization peripheral blood, the average expression of CCR5 on the surface of CD4 + and CD8 + T cells in peripheral blood after mobilization of rhG-CSF showed no significant change, but showed significant inconsistency between different individuals. In 34 (50%) donors, CCR5 expression was down-regulated in 50% of CD4 + cells and remained unchanged or up-regulated in 50%, while expression of CCR5 in 42 (61.8%) donor CD8 + T cells was down- Change or increase. Analysis of 62 transplantable patients for evaluation showed that the incidence of grade II-IV aGVHD was significantly decreased in donor CD4 + T cells (16.6% vs 43.3%, P = 0.032) compared with those in untreated recipients, while CD8 + The cumulative incidence of grade II-IV aGVHD in T cell CCR5 downregulation group was higher than that in non-downregulation group (37.8% vs 16.0%, P = 0.065). CONCLUSIONS: Mobilization of rhG-CSF affects the expression of CCR5 on T cells, and these effects may affect the migration of T cells in vivo and reduce the accumulation of T cells into target organs of GVHD, thus reducing the incidence of aGVHD after allo-HSCT.
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