骨髓腔内供者淋巴细胞输注对移植物抗宿主病的影响

Influence of intra-bone marrow injection with donor lymphocyte upon the development of graft-versus-host disease

观察骨髓腔内供者淋巴细胞输注(IBM-DLI)对异基因小鼠外周造血干细胞移植(allo-PBSCT)后移植物抗宿主病(GVHD)的影响。雌性C57BL/6小鼠为受鼠,接受全身照射(TBI)预处理后,输注雄性BABL/c小鼠来源的经rhG-CSF动员后的外周造血干细胞,分别经尾静脉(IV)和骨髓腔内进行DLI,建立异基因GVHD模型,观察移植后小鼠的生存状态和GVHD发生情况,应用流式细胞仪检测CD4+CD25+调节性T细胞(Treg)比例。结果显示,IBM-DLI组的受鼠GVHD发生比例和严重程度较IV-DLI组明显减低(P<0.01);与IV-DLI组比较,脾细胞中Treg比例在IBM-DLI组明显升高(P<0.01)。实验表明与IV-DLI相比,IBM-DLI有利于减轻GVHD的发生,其机制可能与受鼠体内Treg比例增高有关。

To investigate the effect of donor lymphocyte infusion （DLI） by intra-bone marrow （IBM） or intravenous （IV） injection on the incidence of graft-versus-host disease（GVHD） after allogeneic peripheral hematopoietic stem cell transplantation （allo-PBSCT）, female C57BL/6 mice used as recipients were received total body irradiation （TBI） on day 0, followed by injection with peripheral hematopoietic stem cells and the from mobilized male BALB/c with the granulocyte-colony stimulating factor （rhCrCSF）, and DLI was performed via IV or IBM injections. The extent of GVHD was compared in recipients received allogeneic IBM-DLI with those received IV DLI, and the percentage of CD4^ ＋ CD25^ ＋ regulatory T cells （Tregs） was detected by flow cytometry. It was found that the frequency and severity of GVHD were reduced in IBM-DLI compared with that of IV-DLI （P〈0. 01）, and the percentage of Tregs detected as CD4^＋ CD25^＋ was significantly higher in recipients treated with IBM-DLI than those treated with IV-DLI（P〈0.01）. It is concluded that IBM DLI could induce the proliferation of Tregs, resulting in alleviating the incidence and severity of GVHD after allo PBSCT.