Tju103和CTLA4-Ig联合诱导主要组织相容复合物半相合小鼠骨髓移植耐受  

Induction of tolerance in MHC haploidentical bone marrow transplantation in mice by combination of Tju103 and CTLA4-Ig

作　　者：陈永乐[1] 郭坤元[1] 李玉华[1] 段连宁[1] 张立诚[1] 严定安[1] 

机构地区：[1]第一军医大学附属珠江医院血液科,广州510282

出　　处：《中华器官移植杂志》2004年第6期364-367,共4页Chinese Journal of Organ Transplantation

基　　金：军队自然科学基金十五重点项目 ( 0 1Z0 50 ) ;广州市自然科学基金重点项目 ( 0 0 10 4 3)

摘　　要：目的　观察吲哚亚甲基异烟腙 (Tju1 0 3)和细胞毒性T淋巴细胞相关性抗原 4免疫球蛋白 (CTLA4 Ig)联合应用 ,对主要组织相容复合物 (MHC)半相合小鼠骨髓移植的植入以及移植后移植物抗宿主病 (GVHD)、移植物抗白血病 (GVL)和抗感染的影响 ;探索一条既能降低GVHD又能保留GVL和抗感染能力的移植途径。方法　体外以受者 (正常CB6F1鼠 ,H 2 bd)抗原为特异性免疫耐受诱导原 ,MHC半相合的供者 (C5 7BL/ 6鼠 ,H 2 b)T淋巴细胞经和Tju1 0 3、CTLA4 Ig共育后 ,与供者骨髓细胞混合输入经预处理的受者体内。观察Tju1 0 3和CTLA4 Ig联合作用对移植后造血重建、GVHD、GVL和抗感染的影响。结果　单纯照射组 (A组 ) :全部 (1 0只 )白血病小鼠于照射后 1 1d内死于造血功能衰竭 ,大部分 (8只 )死于照射后 4～ 7d。环磷酰胺 (CTX)治疗组 (B组 ) :全部 (1 0只 )小鼠于接种白血病细胞后 1 6～ 2 3d(移植后 1 1～ 1 8d)死于白血病 ,但CTX治疗延长了白血病小鼠存活期。单纯移植组 (C组 ) :全部 (1 0只 )小鼠于移植后 2 1d内死亡 ,均死于GVHD。CsA预防组 (D组 ) :4只小鼠于移植后 8～ 2 2d内死亡 ,其中 1只死于白血病 ,2只死于感染 ,1只死于GVHD ;6只存活超过30d。Tju1 0 3处理组 (E组 ) :4只小鼠于移植后 9～ 2 6d内死亡 ,?Objective To observe the effect of combination of Tju103 and CTLA4-Ig on engraftment, graft versus host disease (GVHD), graft versus leukemia (GVL) and anti-infection post major histocompatibility complex (MHC) haploidentical bone marrow transplantation in mice in order to seek an effective access to transplantation with less GVHD and more potential GVL and anti-infection.Methods In the presence of the recipient's antigen (normal CB6F1, H-2 bd) as a stimulus for induction of specific immune tolerance, T cells from the MHC haploidentical donors (C57BL/6, H-2 b) were first in vitro cultured with Tju103 and CTLA4-Ig, then were transfused with the donors' bone marrow cells into the preconditioned recipients. At last, the effect of combination of Tju103 and CTLA4-Ig on hematopoietic rebuilding, GVHD, GVL and anti-infection was observed in compared with CsA, Tju103 and CTLA4-Ig as controls.Results The only irradiated group (group A): All the mice (10 mice) died of failure of hematopoiesis within 11 days post irradiation, of which most (8 mice) died within 4～7 days post transplantation. The CTX-treated leukemia group (group B): All the mice (10 mice) died of leukemia within 16～23 days post leukemia cells infusion (11～18 days post BMT). CTX treatment prolonged the survival time. The only transplanted group (group C): The mice began to die from day 16 post transplantation, and all (10 mice) died of GVHD within 3 weeks. The CsA prophylaxis group (group D): 4 mice died within 8～22 days after transplantation, of which one died of leukemia, two died of infection and one died of GVHD, and the remaining 6 survived over 30 days post transplantation. The Tju103 treated group (group E): 4 mice died within 9～26 days post transplantation, of which one died of leukemia, one died of infection and two died of GVHD, and the remaining 6 mice survived over 30 days post transplantation. The CTLA4-Ig treated group (group F): 3 mice died within 14～23 days after transplantation, of which one died of infection and two died

关 键 词：TJU103 GVHD 移植后 小鼠 CTLA4-IG GVL 白血病 存活 共育 抗感染能力 

分 类 号：R457.7[医药卫生—治疗学]