Xu Kai-lin, Zhu Feng, Du Bing, Gao Fei, Cheng Hai, Pan Xiu-ying
Department of Hematology, Affiliated Hospital of Xuzhou Medical College, Xuzhou 221002, China.
Zhonghua Xue Ye Xue Za Zhi. 2007 May;28(5):303-7.
To study the effect of lentiviral vector mediated herpes simplex virus-thymidine kinase/ganciclovir (HSV-TK/GCV) on graft- versus-host disease (GVHD) after allogeneic bone marrow transplantation (allo- BMT) in mice.
Donor splenic lymphocytes from C57BL/6 which were infected by lentiviral vectors carrying HSV-TK were transplanted into 60Co gamma ray irradiated recipient mice with donor bone marrow cells. GCV 25 mg x kg(-1) x d(-1) was administered in 3 groups on day 0, +7, +12 respectively after transplant for 7 days by intraperitoneal injection. Survival time, severity of GVHD, incidence of GVHD, T lymphocytes immune reconstruction and of allogeneic chimerism ratio were detected after allo-BMT.
The average survival times for GCV 0 day, +7 day and +12 day group were (30. 10 +/- 5.21) d, (36.40 +/- 5.28) d and (28.20 +/- 4.82) d respectively, being significantly longer than that in the control group [(15.10 +/- 0.43) d] (P < 0.05). The 50 d-survival rate for TK/GCV + 7 day group was 60%. While for 0 day and +12 day group was 40% and 30% respectively. The incidence of grade III approximately IV GVHD in the control group was 100%, and the dead mice in experimental groups showed pathological changes of II approximately III GVHD. Long-term alive recipient mice only developed grade I approximately II GVHD after allo-BMT. The number of CD4+ lymphocytes in experimental groups was higher than that in control group (P <0.05), but CD8+ lymphocytes was lower on day +5, +10, +15 day (P <0.05). Allogeneic chimerism rate of recipient mice on +30 d was 100%.
HSV-TK/GCV induced by the lentiviral vectors has a definite effect in prevention of GVHD after allo-BMT. GCV administrated from 7 days post-transplantation showed the best effects.
研究慢病毒载体介导的单纯疱疹病毒胸苷激酶/更昔洛韦（HSV-TK/GCV）对小鼠异基因骨髓移植（allo-BMT）后移植物抗宿主病（GVHD）的影响。
将携带HSV-TK的慢病毒载体感染的C57BL/6供体脾淋巴细胞与供体骨髓细胞一同移植到经60Coγ射线照射的受体小鼠体内。移植后第0天、+7天、+12天，分别对3组小鼠腹腔注射更昔洛韦25mg·kg-1·d-1，共7天。检测allo-BMT后小鼠的生存时间、GVHD严重程度、GVHD发生率、T淋巴细胞免疫重建及异基因嵌合率。
更昔洛韦0天组、+7天组和+12天组的平均生存时间分别为（30.10±5.21）天、（36.40±5.28）天和（28.20±4.82）天，均显著长于对照组[（15.10±0.43）天]（P<0.05）。TK/GCV+7天组的50天生存率为60%，而0天组和+12天组分别为40%和30%。对照组III～IV级GVHD的发生率为100%，实验组死亡小鼠表现为II～III级GVHD的病理改变。长期存活的受体小鼠allo-BMT后仅发生I～II级GVHD。实验组CD4+淋巴细胞数量高于对照组（P<0.05），但在+5天、+10天、+15天时CD8+淋巴细胞数量低于对照组（P<0.05）。受体小鼠+30天时的异基因嵌合率为100%。
慢病毒载体介导的HSV-TK/GCV对预防allo-BMT后的GVHD有确切作用。移植后7天开始使用更昔洛韦效果最佳。
