CTLA-4Ig与ICAM-1单抗联合DCp诱导同种移植耐受  

Combined treatment of allograft recipients with CTLA-4 Ig and anti-ICAM-1 mAb plus transfusion of donor-specific DC progenitors

作　　者：丁国善[1] 傅志仁[1] 王全兴[1] 张明[1] 刘玉杉[1] 

机构地区：[1]第二军医大学长征医院器官移植中心,上海200003

出　　处：《第二军医大学学报》2004年第8期849-851,共3页Academic Journal of Second Military Medical University

基　　金：国家自然科学基金(39870809).

摘　　要：目的:利用细胞毒性T淋巴细胞相关抗原4 Ig融合蛋白(CTLA-4 Ig)和细胞问黏附分子1(ICAM-1)单克隆抗体联合治疗经供者树突状细胞前体(DCp)免疫的移植受者诱导移植耐受。方法:实验分4组:对照组、CTLA-4 Ig组、ICAM-1单抗组和联合组,每组8只BALB／c受鼠。每组均以2×106C57BL／6供者DCp经尾静脉输注受鼠。CTLA-4 Ig组和ICAM 1单抗组分别自DCp输注之日起连续2周向受鼠腹腔内注射CTLA-4 Ig或ICAM-1单抗(0.1 mg／d);联合组以同样剂量两药注射2周;对照组则仅输注DCp。DCp输注1周后4组均行异位心脏移植并观察移植心存活时间,进一步作皮肤移植确认耐受状态。结果:对照组、ICAM-1单抗组和CTLA-4 Ig组的C57BL／6供心平均存活时间分别为(20.13±1.64)d、(45.00±2.62)d和(90.00±3.07)d,联合组8例中除1例存活98 d外,其他7例均超过100 d。前3组C57BL／6来源皮肤平均存活时间分别为(4.25±0.89)d、(9.00±0.76)d和(44.50±3.42)d,联合组8例中1例存活91 d,3例存活95 d,其他4例均超过100 d。结论:在供者DCp输注受者后以ICAM-1单抗和CTLA-4 Ig联合处理受者能够诱导针对供者的耐受状态。Objective:To induce donor-specific tolerance in allograft recipients by combined treatment with CTLA-4 Ig and anti-ICAM-1 mAb plus transfusion of donor-specific DC progenitors (DCp). Methods : Thirty-two BALB/c mice were divided into 4 groups: control, CTLA-4 Ig group, ICAM-1 mAb group,and combined treated group.Seven days before cardiac transplantations,donor-derived DCp were transfused to recipients with or without injections of anti-ICAM-1 mAb,CTLA-4 Ig,or both for the following 2 weeks. Thirty days after the cardiac transplant)a second grafting with skin obtained from donor or C3H third-party mice was performed. Results: The survival times of the cardiac allograft in control ,ICAM-1 mAb and CTLA-4 Ig groups were(20. 13 ± 1. 64)d, (45. 00 ± 2. 62) d,and(90. 00±3. 07) d,respectively. Combined treatment led to an indefinite survival of the cardiac allografts ,with 7 of 8 mice survived for more than 100 d. The survival of the second skin allograft were (4. 25 ± 0. 89) d, (9. 00 ± 0. 76) d,and (44. 50±3. 42) d in control, ICAM-1 mAb and CTLA-4 Ig groups ,respectively, with 4 of 8 mice survived for more than 100 d in the combined treated group. Conclusion: CTLA-4 Ig and anti-ICAM 1 mAb synergistically augment the tolerance induction effect of GM-CSF-stimulated bone marrow-derived DCp.

关 键 词：细胞毒性T淋巴细胞相关抗原 4 IG融合蛋白 细胞间黏附分子1 抗体 单克隆 树突状细胞前体 移植耐受 

分 类 号：R392.4[医药卫生—免疫学]