γ射线照射单倍型供者淋巴细胞输注抗白血病作用的实验研究

Study of graft versus leukemia activity of γ ray irradiated haplomismatched donor lymphocytes infusion

目的 探讨 7.5Gyγ射线照射单倍型供者淋巴细胞输注 (DLI)的体内抗白血病作用。方法 荷L61 5白血病 61 5(H 2 k) /BALB/c(H 2 d)F1小鼠 ,于接种L61 5白血病细胞后第 3天接受环磷酰胺(CTX ,2 0 0mg/kg)化疗 ,分别于化疗后第 3 ,5,7天输注 1× 1 0 7经 7.5Gyγ射线照射的亲代BALB/c(H 2 d)小鼠脾淋巴细胞 ,观察抗白血病作用。结果 单倍型供鼠脾淋巴细胞体外经 7.5Gyγ射线照射后 ,增殖能力趋于消失 ,而细胞毒活性增强。输注给荷瘤L61 5CF1小鼠后 ,受鼠的生存期延长为 (1 5.4± 1 .2 )d ,与CTX化疗对照组比较 ,差异具有显著的统计学意义 (t=1 0 .0 3 ,P <0 .0 0 1 ) ,且无严重移植物抗宿主病 (GVHD)发生。结论 7.5Gyγ射线照射单倍型供者淋巴细胞输注能够在减轻GVHD发生的同时 ,保留抗白血病作用 ,为延迟或预防白血病复发提供一种简便易行的方法。

Objective To explore graft versus leukemia activity of 7.5?Gy γ ray irradiated haplomismatched donor lymphocytes infusion(DLI). Methods L615 cells loaded 615(H2 k)/BALB/c(H 2 d)F 1 mice were infused with irradiated haplo mismatched donor lymphocytes at 3,5,7 days after CTX(200?mg/kg) treatment which was given at the 3rd day after L615 cells inoculation. Results T cells irradiated with 7.5?Gy γ ray lost their proliferative capacity but preserved their cytotoxic activity against allogeneic targets.Survival of these recipient mice was longer than that of control(t=10.03,P<0.001) with no severe graft versus host disease(GVHD). Conclusion 7.5?Gy γ irradiation attenuated the GVHD inducing potential of allogeneic lymphocytes while preserving their graft versus leukemia activity.It provides a simple modality to postpone and prevent leukemia relapse.