B7反义肽预处理脾细胞诱导异基因嵌合体形成及延长移植物存活  

Allogeneic chimerism induced by B7 antisense peptide pre-treated splenocytes prolongs the survival of allograft in mice

作　　者：陈晋[1] 张瑞华[1] 刘全胜[1] 储以微[1] 何球藻[1] 熊思东[1] 

机构地区：[1]复旦大学上海医学院免疫学系教育部分子医学重点实验室上海基因免疫与疫苗研究中心,上海200032

出　　处：《中华医学杂志》2004年第2期138-141,共4页National Medical Journal of China

基　　金：国家重点基础研究发展计划资助项目(2 0 0 1CB5 10 0 0 6) ;上海市科技发展基金资助项目 (0 3JC14 0 85 ) ;复旦大学研究生创新基金资助项目

摘　　要：目的　尝试以B7 CD2 8/CTLA4为靶点 ,用B7反义肽 (B7AP)预处理供者的脾细胞 ,免疫受者后结合输注供者骨髓细胞 ,诱导受体形成异基因嵌合体。方法　每只用 5× 10 6/ 10 0 μlB7AP预处理的供者小鼠 (C5 7BL/ 6 )脾细胞免疫受者小鼠 (BALB/c) ,诱导特异性同种低免疫应答反应 ;在此基础上每只受者小鼠输注供者骨髓细胞 2× 10 7/ 10 0 μl,诱导受者形成异基因嵌合体 ,以流式细胞术 (FACS)连续动态监测嵌合状态的维持情况并用小鼠心肌移植模型研究移植物存活的影响因素。结果　在受者体内成功诱导出了特异性同种低免疫应答反应 ,应答水平只有正常未免疫组的 4 3%(n =6 ,P <0 0 0 1) ;嵌合状态可以维持到 10 0d以上 (n =6 ) ,15 0d时嵌合率仍有 3.4 5 % ;嵌合小鼠进行同种异体小鼠心肌移植存活超过 10 0d(n =6 ) ,而对照组阿霉素组只能延长至 16d(n =6 )。结论　B7AP预处理小鼠脾细胞可诱导形成异基因嵌合体 ,并显著延长同种小鼠心肌移植存活的时间 ,为移植免疫的研究提供了一个简单易行的嵌合体平台技术 ,也为用B7AP在移植免疫中的应用进行了有益的尝试。Objective To investigate the roles of B7 antisense peptide (B7AP) in blocking the CD28 -B7 pathway and inducing the allogeneic chimerism. Methods B7 antisense peptide was synthesized by solid phase synthetic methods and purified with HPLC. The C57BL/6 splenocytes of mice were pre-treated by B7AP, and subsequently injected in travenously to BALB/c mice. Three days later the mice were injected with fresh-made bone marrow cells derived from C57BL/6 mice. The B7 expression and allogeneic chimerism were analyzed with FACS. The lymphocyte proliferation reaction and the mice pinna cardiac transplantation model were exerted to study the relation between chimerism and prolongation of allograft in vitro and in vivo. Results Lymphoproliferation of the splenocytes derived from BALB/c mice immunized with the B7AP pretreated C57BL/6 splenocytes versus splenocytes from C57BL/6 mice was inhibited dramatically with a inhibition rates up to 43%. Under this condition, the allogeneic chimerism was successfully induced after BMT. Both the chimerism and the survival of allogeneic cardiac grafts were prolonged over 100 days ( n =6). Conclusion Synthetic B7 antisense peptide can induce allogeneic chimerism in mice and consequently prolong the survival of allogeneic cardiac grafts.

关 键 词：B7反义肽 预处理 脾细胞 异基因嵌合体 同种异体移植 移植免疫学 

分 类 号：R392.1[医药卫生—免疫学]