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目的在骨髓移植的嵌合体中,研究供者骨髓来源的T淋巴细胞对移植物抗宿主性疾病(graft-vs.-host disease,GVHD)是否具有保护作用。方法采用T细胞去除(T cell-depleted,TCD)的Balb/c小鼠与野生型(wild type,WT)B6或TCD B6小鼠的混合骨髓细胞,输入致死量照射(8 Gy)的Balb/c小鼠体内,建立TCD Balb/c+WT B6及TCD Balb/c+TCD B6的混合嵌合体(mixed chimeras,MCs)小鼠模型。8周后,输入WT B6或SJL B6小鼠的脾细胞作为供者淋巴细胞输入(donor lymphocyte infusion,DLI)。通过比较死亡率、体质量变化、GVHD靶器官的病理损害,明确供者骨髓来源的T细胞是否减轻了DLI诱导的GVHD作用。并通过比较骨髓来源的T细胞或DLI来源的T细胞在外周血中的比例,明确骨髓来源的T细胞是否抑制了具有同种异基因反应的DLI来源的T细胞,进一步建立TCD Balb/c+CD4去除的B6或TCD Balb/c+CD8去除的B6的混合嵌合体,分别比较CD4 T或CD8 T细胞对GVHD的抑制作用。结果在含有骨髓来源的T细胞的WT嵌合体中,小鼠的生存率明显高于TCD嵌合体,而DLI后的体质量改变以及GVHD靶器官的损害程度明显轻于TCD嵌合体。而且,骨髓来源的T细胞,可抑制具有同种异基因反应的DLI来源的T细胞。同时,供者骨髓来源的CD4 T或CD8 T细胞对GVHD都起到保护作用,尤其是CD8 T细胞的保护作用更为明显。结论在DLI诱发的GVHD的混合嵌合体中,供者骨髓来源的T细胞,尤其是CD8 T细胞,有效的保护了GVHD的发生。
Objective To investigate whether donor bone marrow-derived T lymphocytes have a protective effect on graft-vs.-host disease (GVHD) in bone marrow-derived chimeras. Methods Balb / c mice with T cell-depleted (TCD) and mixed bone marrow cells from wild-type (WT) B6 or TCD B6 mice were treated with lethal irradiation (8 Gy) of Balb / c mice, a mixed chimeras (MCs) mouse model of TCD Balb / c + WT B6 and TCD Balb / c + TCD B6 was established. Eight weeks later, splenocytes from WT B6 or SJL B6 mice were used as donor lymphocyte infusion (DLI). By comparing the mortality, body mass changes, pathological lesions of target organs of GVHD, it was clarified whether donor bone marrow-derived T cells reduced DLI-induced GVHD. And by comparing the ratio of bone marrow-derived T cells or DLI-derived T cells in peripheral blood, whether T-cells derived from bone marrow-derived T cells inhibit DLI-derived T cells with allogeneic responses was determined to further establish TCD Balb / c + CD4-depleted B6 or mixed chimera of TCD Balb / c + CD8-removed B6 to compare the inhibitory effect of CD4 T or CD8 T cells on GVHD, respectively. Results In WT chimera containing bone marrow-derived T cells, the survival rate of mice was significantly higher than that of TCD chimeras. However, the body mass changes after DLI and the degree of damage to target organs of GVHD were significantly lower than those of TCD chimeras. Moreover, bone marrow-derived T cells can suppress DLI-derived T cells that have allogeneic responses. At the same time, the donor bone marrow-derived CD4 T or CD8 T cells play a protective role in GVHD, especially the protective effect of CD8 T cells is more obvious. Conclusions In mixed chimeras of GVHD induced by DLI, donor bone marrow-derived T cells, especially CD8 T cells, effectively protected GVHD.