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  

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

作　　者：杜峻峰[1] 李世拥[1] 季锡清[1] 陈纲[1] 白雪[1] 陈光[1] 魏晓军[1] 于波[1] 

机构地区：[1]北京军区总医院普通外科全军普通外科中心,100700

出　　处：《中华普外科手术学杂志（电子版）》2012年第2期35-37,共3页Chinese Journal of Operative Procedures of General Surgery(Electronic Edition)

基　　金：国家自然科学基金资助项目(81000189;81101860)

摘　　要：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)dvs.(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7d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。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× 10^6 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 ＋ Te subpopulation in recipients＇ draining lymph nodes were found upregnlated significantly postoperation 7d in treatment group [ （ 19.5 ±5.1 ） % vs. （ 8.70 ± 3.14 ） %, 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 a11orecognition, 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.

关 键 词：输血 抗原 CD 细胞凋亡 移植耐受 动物实验 

分 类 号：R392[医药卫生—免疫学]