中文摘要：

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（11cell-depleted，TCD）的Balb／c小鼠与野生型（wildtype，WT）B6或TCDB6小鼠的混合骨髓细胞，输入致死量照射（8Gy）的Balb／c小鼠体内，建立TCDBalb／c＋WTB6及TCDBalb／c＋TCDB6的混合嵌合体（mixed chimeras，MCs）z]s鼠模型。8周后，输入WTB6或SJLB6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TCDBalb／c＋CD4去除的B6或TCDBalb／c＋CD8去除的B6的混合嵌合体，分别比较CD4T或CD8T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CD4T或CD8T细胞对GVHD都起到保护作用，尤其是CD8T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CD8T细胞，有效的保护了GVHD的发生。

英文摘要：

This study designed to evaluate the protect effects of donor BM-derived T cells against GVHD in established mixed chimeras （MCs）. Firstly, MCs were prepared by injecting a mixture of bone marrow cells from T cell-depleted （TCD） syngeneic Balb/c and allogeneic WT or TCD B6 into lethally irradiated （8 Gy） Balb/c mice. In MCs of TCD Balb/c＋WT B6 or TCD Balb/c＋TCD B6, donor lymphocyte infusion （DLI） was performed using spleen cells from WT B6 or SJL B6 donors 8 weeks after initial TCD BMC injection. Thus, survival rate, body weight change, and GVHD pathology of lung were compared to identify if BM-derived T cells can alleviate GVHD induced by DLI. The proportion of BM-derived T cells or DLI-derived T cells was detected by flow eytometry to research if BM-derived T cells can inhibit allo-reactive DLI-derived T cells. Furthermore, MCs of TCD Balb/e＋CD4 depleted B6 or TCD Balb/c＋CD4 depleted B6 were established to compare the inhibitory effects of CD4 and CD8 T cells against GVHD. The results showed that survival rate was significantly higher in established MCs containing BM- derived T cells when compared to MCs with TCD B6; the lack of donor BM-derived T cells was markedly associated with body weight change and accumulation increase of DLI-derived allo-reactive T cells in parenchymal GVHD target tissues. Moreover, BM-derived T cells could inhibit allo-reactive DLI-derived T cells. From above, we concluded although both CD4 and CD8 T cells contributed to the protection, the latter were significantly more effective. These data represents BM-derived T cells, especially CD8 T cells, offer a potential therapeutic target for preventing and ameliorating GVHD in the setting of DLI in established mixed chimeras.