不同成分淋巴细胞输注对荷瘤小鼠异基因骨髓移植的影响  

Effect of heterogenous DLI on tumor-bearing mouse treated with allo-BMT

作　　者：方烨[1] 刘文超[1] 薛妍[1] 张红梅[1] 黄颖[1] 斯晓明[1] 程捷[1] 

机构地区：[1]第四军医大学西京医院肿瘤中心,陕西西安710033

出　　处：《第四军医大学学报》2006年第17期1566-1569,共4页Journal of the Fourth Military Medical University

基　　金：国家自然科学基金(30471944)

摘　　要：目的建立荷瘤小鼠非清髓异基因骨髓干细胞移植模型,探讨不同成分的供者淋巴细胞输注(DLI)对移植效果的影响及抗肿瘤机制.方法受者鼠为Balb/c(H-2Kd)小鼠,供者鼠为C57bl/6(H-2Kb)小鼠,受者小鼠腹腔接种小鼠肝癌细胞株H22细胞,观察腹水生成情况及生存状况.于接种瘤细胞后d5给予全身照射预处理,随后给受者小鼠尾静脉输注供者鼠的骨髓细胞,建立荷瘤小鼠的MHC不相合亚移植模型.依据不同DLI将荷瘤鼠受者鼠随机分为A,B,C,D,E组,每组10只.A,B,C,D组均给予预处理,A组预处理后于移植d1,7给予供者小鼠全脾细胞0.5×107个;B组分别于移植d1,7给予去除CD8+细胞供者鼠脾细胞0.5×107个;C组于移植d1,7给予去除CD4+细胞供者鼠脾细胞0.5×107个;D组只接受预处理不作移植及DLI;E组为对照组,既不作预处理,也不接受骨髓细胞移植及DLI.观察各组成瘤率、生存期、嵌合状态、造血恢复情况及移植物抗宿主病(GVHD).结果所有小鼠均产生腹水,成瘤率100%;生存期C组最长为(35.6±3.1)d,B组为(23.7±10.9)d,B,C两组相比有统计学差异(P<0.05);接受移植的A,B,C组嵌合率均高于0.80,只接受预处理的D组鼠白细胞计数自行恢复正常;GVHD评分C组与B组有明显差异(P<0.05).结论建立非清髓荷瘤小鼠异基因骨髓干细胞移植模型条件适宜,说明去除CD4+细胞的DLI能够有效地减轻GVHD反应,延长荷瘤鼠生存期;去除CD8+细胞的DLI会加重GVHD反应,影响移植.AIM： To cstablish a tumor-bearing mouse model of allogenic bone marrow transplantation （allo-BMT） with nonlethal preconditioning, to observe the anti-tumor effect of heterogenous donor lymphocyte infusion （DLI） after allo-BMT and to research the mechanism, METHODS： Recipient mouse was Balb/c （H- 2K^d）, and donor was C57bl/6 （H-2K^b）. Hepatoma H22 cells were injected into the abdominal cavity of all recipient mice, and after that the living status was observed. Five days later, the recipients were treated with preconditioning （ TBI 3 Gy ＋ CTX 200 mg/kg）. The bone marrow cells of the donors were transplanted to the recipients via vena caudalis. Fifty recipient mice were divided evenly into 5 groups （A, B, C, D and E groups） at random, according to different DLI. Group A was injected 0.5 × 10^7 whole spleen cells from donor mice on day 1, 7 after transplantation ; group B was injected 0.5 × 10^7 CD8^＋T-cell-depleted spleen cells from donor mice on day 1, 7; group C was injected 0.5 × 10^7 CD4 ＋ T-cell-depleted spleen cells from donor mice on day 1, 7; group D, as control group, was just preconditioned but not transplanted or DLI; group E, the blank control group, was neither preconditioned neither transplanted nor DLI. After that life span, the chimerism, hematopoiesis recovery and graft versus host disease （GVHD） were observed. RESULTS： All recipients showedascites. Life span of group E was （20. 1 ＋3.4） d, shorter than the others. The group C had a longest life span [ （35.6 ± 3. 1 ） d ]. Statistical difference was found between group B and C in life span （P 〈 0.05）. The chimerism of group A, B and C was above 80%. The hematopoiesis of group D （ control group） , recovered under no interference. The hematopoiesis recovery of group B was slower than the others. The GVHD scores of group B were higher than those of group A and C. Statistical difference was found between group B and C in GVHD scores （ P 〈 0.05 ）. CONCLUSION ： The nonlethal preconditi

关 键 词：骨髓移植 淋巴细胞输注 移植物抗宿主病 嵌合状态 

分 类 号：R457.7[医药卫生—治疗学]