同种异基因Th2细胞移植对GVHD和GVL效应的作用

Effects of Allogeneic Transplantation of T Helper-2 Cells on Graft-versus-Host Disease and Graft-versus-Leukemia Effect

为探讨同种异基因Th2细胞移植是否可以减低移植物抗宿主病 (GVHD)的发生和保留移植物抗白血病 (GVL)效应的作用 ,在体外用rmIL 4 ,ConA和离子霉素把供鼠 (C5 7BL/ 6 H 2b)T细胞优势化诱导培养为Th2细胞 ,再把Th2细胞与供鼠骨髓细胞混合移植给红白血病受鼠模型(EL96 11H 2d)。结果表明 :未处理的对照组 ,受鼠平均存活时间为 (10 .6± 1 3)天 ,10只均死于白血病 ;环磷酰胺化疗组 ,小鼠平均存活 (18 7± 4 2 )天 ,10只小鼠最终均死于白血病 ;骨髓细胞和脾T淋巴细胞移植组 ,小鼠平均存活 (2 2 7± 7 4 )天 ,9/ 10只均死于GVHD ;骨髓细胞和Th2细胞移植组 ,3/ 10只在 2 8天内死于GVHD ,其余 7/ 10只无GVHD发生 ,白血病发病时间明显推迟 ,平均存活 (36 9± 10 8)天 ,在 5 0天时检查有 2只鼠无白血病证据。研究证明体外极向化诱导培养的Th2细胞移植可减低GVHD发生的同时保留了抗白血病的能力。

This study was undertaken to explore whether the graft-versus-host-disease could be decreased and graft-versus-leukemia effect be retained by transplantation of allogeneic T helper-2 (Th2) cells. T cells from C57BL/6 H-2b mice were incubated and polarized with rmIL-4, Con A and ionomycin in vitro, and then, the T cells were mixed with marrow cells and transplanted into recipient BALB/c H-2d mice bearing erythroleukemia cells. The occurence of GVHD and GVL effect was observed. The results showed that the mean survival time in the groups of untreated control, cyclophosphamide treatment, marrow and spleen T cell transplantation and marrow and Th2 cell transplantation was 10.6±1.3, 18.7±4.2, 22.7±7.4 and 36.9±10.8 days, respectively. In untreated control and cycophosphamide treatment groups, all of ten mice died from leukemia. Nine of ten mice died from GVHD in marrow and spleen T cells transplantation group. In marrow and spleen Th2 cell transplantation group, three of ten mice died from GVHD, and GVHD was not occurred in the other seven mice, and there was no any evidence of leukemia in two mice on 50 days after transplantation. It was concluded that tranplantation with polarized Th2 cells could relieve GVHD, and at the same time retain the GVL effect.