缺乏可诱导共刺激信号的供体特异性输血促进受体鼠T细胞凋亡的体内研究

目的 探讨缺乏可诱导共刺激分子(ICOS)/B7h信号的供体特异性输血(DST)对异基因小鼠心脏移植术后T细胞(Tc)凋亡的影响.方法 按陈氏方法建立小鼠颈部异位心脏移植模型,术后统计各组移植物的存活时间.实验分3组,异基因组:分别以BALB/c和C57BL/6为供、受体,不予治疗;同基因组:供、受体均为C57BL/6,不予治疗;治疗组:以BALB/c和C57BL/6为供、受体,给予治疗.通过流式细胞术检测受体鼠外周血CD8+ICOS+Tc亚群比例以及受体鼠引流淋巴结中CD8+Tc的凋亡情况.结果 与异基因组比,治疗组中心脏移植物存活时间明显延长[(84.4±29.1) d vs.(7.0±0.8) d,P＜0.01].与异基因组比,治疗组外周血CD8+Tc亚群无明显缩减,而在CD8+ICOS+Tc亚群中,治疗组中显著低于异基因组[(7.5±2.0)% vs.(14.0±3.0)%,P＜0.05].与异基因组比,治疗组受体移植术后7 d引流淋巴结中CD8+Tc凋亡比例显著上调[(19.5±5.1)% vs.(8.7±3.1)%,P＜0.05].结论 通过ICOS/B7h信号的供体特异性输血预处理可以诱导引流淋巴结中CD8+Tc凋亡,这与受体外周血中CD8+ICOS+Tc亚群变化相关,可能在耐受的诱导过程中起重要作用.

Apoptosis of peripheral T cells in rodent cardiac allograft recipients induced by donor specific transfusion with Impaired ICOS/B7h allorecognition

Objective To investigate apoptosis of CD8+T cells(Tc) subpopulation in rodent cardiac allograft recipients,which were treated by donor specific transfusion combined with blockade of ICOS/B7h costimulation.Methods Mice were assigned to three groups:In allogeneic group,donor hearts were harvested from BALB/c mice,and allografts were heterotopically transplanted in the neck of C57BL/6 using Chen’s technique,without treatment.In isogeneic group,both donors and recipients were BALB/c mice,which underwent graft transplantation without treatment.A combination of 5×106 ICOS-Fc-targeted B cells on day 0 and 10mg/kg/d ICOS-Fc on day 0-6 were given in treatment group.Both percentage of CD3+CD8+ICOS+Tc in recipients’ peripheral blood and apoptosis of CD8+Tc in recipients’ draining lymph nodes were detected by FCM.Results In comparison with allogenic group,the survival of cardiac grafts could be prolonged by the combination treatment [(84.4±29.1) d vs.(7.0±0.8) d,P<0.01].In treatment group,CD8+Tc clone size remained stable in recipients’ peripheral blood,however,the percentage of CD3+CD8+ICOS+Tc decreased significantly compared with that in allogenic group [(7.5±2.0)% vs.(14.0±3.0)%,P<0.05].In comparison with allogenic group,apoptosis of CD8+Tc subpopulation in recipients’ draining lymph nodes were found upregulated significantly postoperation 7d in treatment group [(19.5±5.1)% vs.(8.7±3.1)%,P<0.05].Conclusions Apoptosis of CD8+Tc in recipients’ draining lymph nodes could be enhanced by the pretreatment of donor specific transfusion with impaired ICOS/B7h allorecognition,which might be associated with the variation of CD3+CD8+ICOS+Tc subpopulation in peripheral blood and might contribute to the induction of allograft tolerance.