摘要
目的联合阻断OX40/OX40L和CD28/B7双协同信号途径和供体特异性脾细胞输注,诱导预存同种反应性记忆T淋巴细胞大鼠对同种心脏移植物的耐受。方法建立大鼠预存同种反应性记忆T淋巴细胞的移植模型,采用免疫磁珠法分选CD8^+CD44^-记忆性T细胞;对过继转移供体特异性CD8^+记忆性T细胞3d的Lewis大鼠分别/合并输注AdCTLA4Ig、AdOX40Ig、供体脾细胞(DST),同时移植来至DA大鼠的心脏;48h后取出心脏进行组织学分析、细胞因子表达分析,同时观察不同处理移植心脏存活时间。结果AdCTLA4Ig+AdOX40Ig+DST组分别与AdCT—LA4Ig、AdOX40Ig和DST比较,心脏组织病理级别较低,白细胞介素(IL)-2及干扰素(IFN)-γ的表达水平也明显比其他组低很多,而心脏存活时间显著延长。结论联合阻断OX40/OX40L和CD28/B7和供体特异性脾细胞输注能较好地诱导大鼠心脏移植物耐受。
Objective To induce the tolerance to cardiac allograft by combined blockade of OX40/OX40L and CD28/B7 co-stimulatory signaling and donor specific spleen cell transfusion in rat models of pre-existent allogenie reactive memory T lymphocytes. Methods Lewis rats that underwent 3 days of adoptive transfer of donor specific CD8^+ memory T cells, separated by immunomagnetic bead separation kit, received either separate or combined transfusion of AdCTLA4Ig,AdOX40Ig, donor spleen cells (DST) and transplantations of hearts of DA rats at the same time. Cardiac allografts were taken out 48 h after transplantation for histological analysis and cytokines expression, and survival time of cardiac allografts with different treatments was observed. Results Compared with AdCTLA4Ig, AdOX40Ig and DST groups, AdCTLA4Ig + AdOX40Ig + DST group showed lower cardiac pathological grade with much lower expression level of IL-2 and IFN-γ, and much longer heart survival time. Conclusion Combined blockade of OX40/ OX40L and CD28/B7 and donor specific spleen cell transfusion could induce rat cardiac graft tolerance.
出处
《中华实验外科杂志》
CAS
CSCD
北大核心
2009年第7期917-919,共3页
Chinese Journal of Experimental Surgery
基金
烟台市科学技术发展计划资助项目(2007139-12)
关键词
心脏移植
记忆T淋巴细胞
免疫耐受
Heart transplantation
Memory T lymphocytes
Immune tolerance