TJU103对小鼠同种异基因造血干细胞移植模型GVHD的预防作用  

Role of TJU103 in prevention of graft-versus-host disease after allogeneic stem cell transplantation in mice

作　　者：王三斌[1] 郭坤元[2] 胡灯明[1] 尹波[1] 

机构地区：[1]成都军区昆明总医院血液科,云南昆明650032 [2]南方医科大学珠江医院血液科,广东广州510282

出　　处：《南方医科大学学报》2006年第6期810-813,共4页Journal of Southern Medical University

摘　　要：目的探讨TJU103对小鼠同种异基因造血干细胞移植模型移植物抗宿主病(GVHD)是否起预防作用。方法(1)用单向混合淋巴细胞培养方法检测TJU103对T淋巴细胞增殖的影响;(2)以BALB/c(H-2d)、CB6F1(H-2d/b)分别作为完全异基因移植和半相合基因移植的受鼠,给予9.0Gy全身照射后4h,单纯照射组经尾静脉注射0.3mlD-Hank's液,不进行细胞移植;对照组经尾静脉注射C57BL/6小鼠混合细胞悬液(4.5×106骨髓细胞+3.0×107脾细胞),但不进行其他治疗处理;实验组经尾静脉注射C57BL/6小鼠混合细胞悬液(4.5×106骨髓细胞+3.0×107脾细胞)+TJU103(终浓度25μg/ml),此后腹腔注射TJU10350μg/d,共7d,然后观察其造血恢复、植入及GVHD的情况。结果(1)TJU103可以显著抑制T细胞活化增殖,其抑制作用呈剂量依赖性,在25μg/ml浓度时,可以抑制83%细胞增殖。(2)由于没有给予GVHD防治措施,对照组受鼠GVHD的发生率和死亡率分别为10/10和10/10;而完全异基因移植实验组小鼠GVHD发生率仅为2/10,30d生存率增加至8/10(P<0.01),中位生存期延长至30d以上(P<0.01);半相合基因移植实验组小鼠GVHD发生率为1/10,30d生存率增加至9/10(P<0.01),中位生存期延长至30d以上(P<0.01)。结论TJU103不仅可以显著抑制体外T淋巴细胞增殖效应,而且可显著降低小鼠同种异基因造血干细胞移植模型GVHD的发生率。Objective To explore the role of TJU 103 in preventing graft-versus-host disease （GVHD） after allogeneic stem cell transplantation in mice. Methods BALB/c mouse splenic lymphocytes were collected and treated by mitomycin as the activating cells and the C57BL/6 mouse splenic lymphocytes as the reacting cells. In the experimental groups, the effect of TJU103 on the proliferative response of T cells was observed. BALB/c（H-2d） and CB6F1 （H-2d/b） mice were used as the MHC-full-mismatched recipients and MHC-haplo-identical recipients, respectively, and pretreated by total body irradiation at 9.0 Gy before transplantation. For the recipients of the irradiation group, 0.3 ml D-Hank＇s solution was injected through the tail vein without cell transplantation, the recipients of the control group received injection of 4.5 × 106 bone marrow cells mixed with 3.0 ×10^7 spleen cells from C57BL/6 mice through the tail vein, and those in the experimental group received cell transplantation in the same manner with also injection via the tail vein of 25 μg/ml TJU 103, which was subsequently injected intraperitoneally for 7 consecutive days at daily dose of 50 μg. The hematopoietic recovery, engratiment and GVHD of the recipients were observed. Results TJU103 resulted in a dose-dependent inhibition of T cell proliferation in mixed lymphocyte reaction （MLR）, and nearly 83% inhibition of the proliferative response was observed with the addition of 25 μg/ml of TJU103. Without any treatment, the occurrence of GVHD and death rate in the control group was both 10/10. Daily injection of TJU 103 at 50 μg for the initial post-transplantation week protected the mice fi＇om GVHD. In the MHC-full-mismatched model, the incidence of GVHD and survival rate on day 30 of the experiment group was 2/10 and 8/10, showing significant difference fi＇om those in the control group （P〈0.01）. The median survival time （MST） was 30 days in the experimental group versus 15 days in the control group （P〈0.05）. In the MHC-ha

关 键 词：TJU103 同种异基因造血干细胞移植 移植物抗宿主病 

分 类 号：R392[医药卫生—免疫学]