抗TCRαβ单克隆抗体联合大剂量供体骨髓细胞输注诱导小鼠皮肤移植耐受的研究  

Study on the induction of skin transplantation tolerance in mice by anti-TCRαβ monoclonal antibody combined with high dose of donor bone marrow cells infusion

作　　者：曹旭东[1] 马建波[2] 刘家望[2] 刘翠青 李爱玲[2] 王光明[2] 谢蜀生[2] 

机构地区：[1]新疆石河子大学医学院,832002 [2]北京大学医学部免疫学系 [3]邢台医专

出　　处：《中华微生物学和免疫学杂志》2003年第11期887-890,共4页Chinese Journal of Microbiology and Immunology

基　　金：国家自然科学基金重点资助项目 (3 983 0 3 40 ) ;北京大学 985 2项目资助

摘　　要：目的　探讨抗TCRαβ单克隆抗体联合大剂量供体骨髓细胞输注方法在同种异基因小鼠皮肤移植耐受诱导中的作用。方法　第 0天 ,C5 7BL 6 (H 2 b,B6 )小鼠尾静脉注入 2× 10 8BALB c(H 2 d,B c)来源的骨髓细胞 ,同时腹腔注射抗TCRαβ单克隆抗体 5 0 0 μg。第 6天进行皮肤移植。在不同的时间对B6小鼠进行迟发型超敏反应测定 ,混合淋巴细胞反应分析 ,并进行MLR的IL 2逆转实验和过继转移实验 ,初步探讨耐受形成机制。结果　抗TCRαβ单克隆抗体联合大剂量供体骨髓细胞输注处理的B6小鼠中供体皮肤移植物平均存活为 5 0 .4d ,显著长于其它各组 (P <0 .0 0 1)。相对于正常对照组小鼠 ,耐受B6小鼠在迟发型超敏反应和混合淋巴细胞反应中均表现出显著的低反应性 (P <0 .0 0 1)。IL 2逆转实验结果表明 ,克隆不应答 (anergy)可能参与了移植耐受的形成。体内、外过继转移实验均显示耐受B6小鼠脾细胞中存在抑制细胞活性。结论　抗TCRαβ单克隆抗体联合大剂量供体骨髓细胞输注可以在组织相容性抗原完全不相同的成年小鼠间成功地诱导出皮肤移植物的长期耐受。多种耐受机制 ,包括克隆不应答、抑制细胞 ,都参与了耐受的形成。Objective To explore the role of anti-TCRαβ monoclonal antibody combined with high dose of donor bone marrow cells infusion in the induction of murine skin allografts tolerance. Methods On day 0, 2×10 8 bone marrow cells (BMC) of BALB/c mouse (H-2 d) were injected into recipient C57BL/6 (H-2 b, B6) mice via the tail vein, meanwhile, an intraperitoneal injection of anti-TCRαβ monoclonal antibody (500μg) was given. Skin grafting was performed on day 6. DTH, MLR, IL-2 reverse assay of MLR and adoptive transfer assay were performed at different time points and tolerance mechanisms were investigated. Results The mean survival time (MST) of BALB/c skin allografts in B6 recipients that were treated by anti-TCRαβ monoclonal antibody combined with high dose of donor bone marrow cells infusion was 50.4 days, which was significantly longer than that in other groups ( P <0.001). DTH and MLR assay indicated that the tolerant mice displayed significant hyporesponsivness against donor antigen ( P <0.001). The result of IL-2 reverse test showed that clone anergy was probably involved in the formation of tolerance in the tolerant B6 mice. In vivo and in vitro adoptive transfer assay, suppressive activity in the spleens of tolerant B6 mice was observed. Conclusion Treatment of anti-TCRαβ monoclonal antibody combined with high dose of donor bone marrow cells infusion can successfully induce a long-term tolerance in BALB/c mice to B6 skin graft. Multiple mechanisms, including clone anergy and suppressor cells were involved in the tolerence.

关 键 词：抗TCRαβ单克隆抗体 大剂量 供体骨髓细胞输注 诱导 小鼠 皮肤 移植耐受 

分 类 号：R373.21[医药卫生—病原生物学]