CD4＋T细胞在CD8＋T细胞介导的排斥反应中的作用

Function of CD4 ＋ T cells in CD8 ＋ T cell mediated rejection

目的 观察在缺乏CD4＋T细胞的辅助作用下,小鼠初始CD8＋T细胞与同种反应性记忆性CD8＋T细胞（CD8＋ Tm）在介导同种异体心脏移植的急性排斥反应中的作用.方法 C57BL/6小鼠为供体,受体为BALB/c源免疫缺陷裸小鼠,采用套管法进行颈部异位心脏移植.受体小鼠随机数字表法分为3组：CD8＋ Tm组（心脏移植前过继同种反应性CD8＋Tm细胞）、CD8＋T组（心脏移植前过继初始CD8＋T细胞）、对照组（只进行心脏移植）,每组6只.心脏移植后记录并且计算移植物生存期;移植后第10天对受体鼠进行免疫学检测,观察其移植物病理改变,淋巴结、脾脏中的CD8＋细胞比例及血清中白细胞介素2（IL-2）的水平.结果 单独过继初始CD8＋T细胞并不能介导心脏移植的排斥反应,移植物平均生存期＞60 d;而过继同种反应性CD8＋ Tm细胞能够介导移植心脏的排斥反应,移植物平均生存期（8.9±0.5）d,差异有统计学意义（P＜0.01）.与未移植小鼠相比,过继转移的初始CD8＋T细胞在受体移植后第10天的脾脏及淋巴结中均没有增殖（2.70％±0.08％比2.27％±0.22％、3.41％±0.25％比2.80％±0.62％,均P＞0.05）;而过继转移的同种反应性的CD8＋ Tm细胞在移植后受体脾脏及淋巴结中比例明显高于未移植小鼠（9.65％±0.60％比2.12％±0.18％、11.15％±1.35％比3.03％±0.10％,均P＜0.01）.CD8＋T组心脏移植前、后血清IL-2分泌水平差异无统计学意义（P＞0.05）;而CD8＋ Tm组移植后能够分泌大量IL-2 （P ＜0.01）.结论 在缺乏CD4＋T细胞辅助作用下,初始CD8＋T细胞不能激活并发挥免疫学作用,同种反应性CD8＋ Tm细胞可以活化、增殖并发挥免疫杀伤作用.

Objective To explore the absence of CD4 ＋T cells,na（i）ve CD8 ＋T cells and memory CD8 ＋ T（CD8 ＋ Tm） cells in the role of mediated acute graft rejection and discuss its possible mechanism.Methods Mice were randomly divided into three groups （n =6）.And at Day 2 pre-transplantation,two types of cells （CD8 ＋ T cells （CD8 ＋ T group） or CD8 ＋ Tm cells（CD8 ＋ Tm group）） were transferred into nude mice （1 × 10^6 cells/one mice） via tail vein injections.At Day 0,C57BL/6 mice were used as donors for cervical heterotopic heart transplantation with nude mice as recipients （control group without transplantation）.The survival of transplants was recorded and the mean survival time （MST） calculated.Then at Day 10 post-transplantation,the recipient＇s heart graft,spleen and lymph node were collected for immunological detections.And the ratio of CD8 ＋ cells in spleen and lymph nodes and serum levels of IL-2 in recipients were tested.Results In the group of adoption na（i）ve CD8 ＋ T cells and heart grafting,there was no occurrence of acute graft rejection（MST 〉 60 d）,while in the group of adoption memory CD8 ＋ Tm cells and heart grafting,there was serious rejection（MST：（8.9 ± 0.5） d） （P 〈0.01）.In the group of adoption na（i）ve CD8 ＋T cells and heart grafting,cell proliferation of transferred CD8 ＋T cells in spleen and lymph node showed no statistical difference compared with non-transplanted mice （2.70% ± 0.08% vs 2.27% ± 0.22%,3.41% ± 0.25% vs 2.80% ± 0.62%,both P 〉 0.05）.However,in the group of adoption CD8 ＋ Tm cells and heart grafting,cell proliferation of transferred CD8 ＋ Tm cells in spleen and lymph node showed significant statistical difference with non-transplanted mice （9.65% ± 0.60% vs 2.12% ±0.18%,11.15% ± 1.35% vs 3.03% ± 0.10%,both P 〈 0.01）.The levels of IL-2 secretion before and after transplantation,na（i）ve CD8 ＋ T cells showed no statistical difference （P 〉 0.05）,CD8 ＋ Tm cells showed significant statistical difference （P 〈 0.01）.Conclusions In the absence of CD4 ＋ T lymphocyte helping,na（i）ve CD8 ＋ T cells can not activate and show immunological functions.But memory CD8 ＋ T can activate,proliferate and generate effector cells to mediate immune response.