CD200/CD200R在异基因造血干细胞移植后的表达水平及意义

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背景:CD200与其受体CD200R均属于免疫球蛋白超家族成员,在体内起到传递免疫信号、参与免疫稳态的维持、调节自身免疫功能紊乱以及抑制巨噬细胞系统的功能。目的:探讨CD200/CD200R在移植物抗宿主病(GVHD)中的作用。方法:将入组患者分为4组:aGVHD组、non-aGVHD组、cGVHD组及non-cGVHD组。首先应用流式细胞术测定各组CD200及CD200R在CD19+细胞、CD3+细胞及树突状(DC)细胞表面表达水平的差异,随后通过实时荧光定量PCR测定各组CD200及CD200R的mRNA表达水平的差异,最后将各研究组外周血单个核细胞与不同浓度的抗-CD200R1抗体体外共培养48 h,采用ELISA方法测定培养上清IL-10水平,以验证CD200/CD200R的功能。结果:non-aGVHD组CD19+细胞表面CD200+表达水平高于aGVHD组,低于正常对照组。non-cGVHD组CD19+细胞表面CD200+表达水平高于正常对照组及cGVHD组。aGVHD组和cGVHD组CD200的mRNA的表达水平均低于正常对照组。aGVHD组CD200的mRNA表达水平低于non-aGVHD组,cGVHD组低于non-cGVHD组。各组CD200R的mRNA表达水平未见明显差异。抗-CD200R1抗体阻断CD200/CD200R通路后,细胞培养上清中IL-10浓度随抗-CD200R1抗体浓度的增加呈下降趋势。结论:aGVHD及cGVHD患者在CD19+CD200+细胞及mRNA表达水平均明显低于未发生GVHD的患者,阻断CD200/CD200R通路后IL-10分泌水平下降,提示CD200/CD200R可能与GVHD的发生有一定的相关性。 BACKGROUND: CD200 and its receptor CD200R are members of the immunoglobulin superfamily, which transmit immune signals in the body, participate in the maintenance of immune homeostasis, regulate autoimmune disorders and inhibit the function of macrophage system. Objective: To investigate the role of CD200 / CD200R in graft-versus-host disease (GVHD). Methods: The patients were divided into 4 groups: aGVHD group, non-aGVHD group, cGVHD group and non-cGVHD group. Firstly, the expression of CD200 and CD200R on the surface of CD19 + cells, CD3 + cells and dendritic cells were detected by flow cytometry. Then the mRNA expression levels of CD200 and CD200R in each group were determined by real-time fluorescence quantitative PCR Finally, the peripheral blood mononuclear cells of each study group were co-cultured with different concentrations of anti-CD200R1 antibody in vitro for 48 h. ELISA was used to determine the level of IL-10 in the culture supernatant to verify the function of CD200 / CD200R. Results: The expression of CD200 + on CD19 + cells in non-aGVHD group was higher than that in aGVHD group and lower than that in normal control group. The expression of CD200 + on CD19 + cells in non-cGVHD group was higher than that in normal control group and cGVHD group. CD200 mRNA expression levels of aGVHD group and cGVHD group were lower than those of the normal control group. The mRNA expression of CD200 in aGVHD group was lower than that in non-aGVHD group and lower in cGVHD group than in non-cGVHD group. There was no significant difference in the mRNA expression level of CD200R in each group. Anti-CD200R1 antibody block CD200 / CD200R pathway, the cell culture supernatant IL-10 concentration decreased with the anti-CD200R1 antibody concentration decreased. CONCLUSION: The expression of CD19 + CD200 + cells and mRNA in aGVHD and cGVHD patients is significantly lower than that in patients without GVHD. The decrease of IL-10 secretion after blocking the CD200 / CD200R pathway suggests that CD200 / CD200R may be associated with the occurrence of GVHD Relevance.
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