半相合供者淋巴细胞输注抗中、高危非霍奇金氏淋巴瘤的实验研究

The study on Haploidentical Related Donor Lymphocyte Infusion Versus High-risk Non-Hodgkin,s Lymphoma in Vitro

目的阐明半相合供者淋巴细胞输注(DLI)抗中、高危非霍奇金氏淋巴瘤(NHL)的机制。方法通过预实验确定输注最佳时间及最佳浓度,并检测此条件下加入去CD8+T细胞和去CD4+T细胞半相合DLs培养后细胞的凋亡率及培养液中白细胞介素-2(IL-2)的浓度。结果在最佳输注时间(培养后24小时)、最佳浓度(2.5×105/ml)下加入去CD8+T细胞半相合DLs进行培养,淋巴瘤细胞凋亡率(17.6±2.5)%与对照组(4.6±1.2)%及加入去CD4+T细胞半相合DLs(5.2±1.6)%相比较,有显著性差异,而且加入去CD8+T细胞半相合DLs的培养液中IL-2浓度显著高于加入去CD4+T细胞者和对照组。结论CD4+T细胞在移植物抗淋巴瘤效应中可能起着比CD8+T细胞更重要的作用,在临床使用中,选择性去除CD8+T细胞,可减少或减轻移植物抗宿主病(GVHD),并且不影响移植物抗淋巴瘤效应。IL-2在半相合DLs发挥移植物抗淋巴瘤效应过程中可能起着重要的作用。

Objective：To elucidate the mechanism of haploidentical related donor lymphocyte infusion anti high-risk non -Hodgkin＇s lymphoma,and to find the optimal infusion time and cell dose in order to provide evidence for clinical application. Methods：By beforehand experiment, we found the optimal time and infusing DLs dose, and under the optimal time and dose, also measured the apoptosis rate when infused non-CD4^＋T lymphocyte and non-CD4^＋T lymphocyte DLs respectively. IL-2 concentration was measured in culture medium. Results： The optimal time is 24 hours,the optimal dose is 2.5×10^5/ml. The difference of apoptosis between non-CD4^＋T lymphocyte infusion and control,non-CD4^＋T lymphocyte infusion is significant.IL-2 concentration of non-CD8^＋T lymphocyte is higher than that of non-CD4^＋T lymphocyte.Conclusion：CD4^＋T lymphocytes may have more important role in GVL than one which CD8^＋T lymphocytes do.so in clinical application,selective deletion of CD8^＋T lymphocyte may reduce GVHD, not interfere with its GVL. And IL-2 may be the major mechanism during GVL in haploidentical related DLs.