中华微生物学和免疫学杂志
中華微生物學和免疫學雜誌
중화미생물학화면역학잡지
CHINESE JOURNAL OF MICROBIOLOGY AND IMMUNOLOGY
2013年
4期
298-302
,共5页
朱杰昌%付蔚华%许翼麟%朱理玮
硃傑昌%付蔚華%許翼麟%硃理瑋
주걸창%부위화%허익린%주리위
调节性T细胞%共刺激通路%树突状细胞%CD40%心脏移植
調節性T細胞%共刺激通路%樹突狀細胞%CD40%心髒移植
조절성T세포%공자격통로%수돌상세포%CD40%심장이식
Regulatory T cell%Costimulatory pathway%Dendritic cell%CD40%Heart transplantation
目的 探讨在输注供者低表达CD40的树突状细胞(dendritic cells,DC)后,调节性T细胞(regulatory T cell,Treg)对小鼠移植心脏的保护作用.方法 以针对小鼠CD40基因的RNA干扰(RNA interference,RNAi)慢病毒载体在体外感染供者骨髓来源的DC,制备低表达CD40的耐受性DC(Tol-DC).建立小鼠异位腹腔心脏移植模型.设置异系对照组、未感染DC组及单纯慢病毒感染DC组.观察各组移植心脏存活时间,评定术后7d移植物排斥反应、病理分级,并以流式细胞术检测手术前后外周血CD4+ CD25+Treg变化水平.结果 CD40-RNAi慢病毒载体在体外感染DC 48 h后,CD40 mRNA表达明显受到抑制,抑制效率为80.9％.CD40表达明显下降,由74.37％ ±4.08％降至40.07％±4.03％ (P＜0.05).与异系对照组和未感染DC组相比,单纯慢病毒感染DC组移植心脏存活时间(14±4)d明显延长(P＜0.01)；术后7d急性排斥反应病理分级均明显降低(P＜0.05)；术后3d、7d外周血CD4+ CD25+ Treg水平均明显升高(P＜0.05).结论 CD4+ CD25+ Treg对输注供者低表达CD40的树突状细胞的小鼠移植心脏具有保护作用.
目的 探討在輸註供者低錶達CD40的樹突狀細胞(dendritic cells,DC)後,調節性T細胞(regulatory T cell,Treg)對小鼠移植心髒的保護作用.方法 以針對小鼠CD40基因的RNA榦擾(RNA interference,RNAi)慢病毒載體在體外感染供者骨髓來源的DC,製備低錶達CD40的耐受性DC(Tol-DC).建立小鼠異位腹腔心髒移植模型.設置異繫對照組、未感染DC組及單純慢病毒感染DC組.觀察各組移植心髒存活時間,評定術後7d移植物排斥反應、病理分級,併以流式細胞術檢測手術前後外週血CD4+ CD25+Treg變化水平.結果 CD40-RNAi慢病毒載體在體外感染DC 48 h後,CD40 mRNA錶達明顯受到抑製,抑製效率為80.9％.CD40錶達明顯下降,由74.37％ ±4.08％降至40.07％±4.03％ (P＜0.05).與異繫對照組和未感染DC組相比,單純慢病毒感染DC組移植心髒存活時間(14±4)d明顯延長(P＜0.01)；術後7d急性排斥反應病理分級均明顯降低(P＜0.05)；術後3d、7d外週血CD4+ CD25+ Treg水平均明顯升高(P＜0.05).結論 CD4+ CD25+ Treg對輸註供者低錶達CD40的樹突狀細胞的小鼠移植心髒具有保護作用.
목적 탐토재수주공자저표체CD40적수돌상세포(dendritic cells,DC)후,조절성T세포(regulatory T cell,Treg)대소서이식심장적보호작용.방법 이침대소서CD40기인적RNA간우(RNA interference,RNAi)만병독재체재체외감염공자골수래원적DC,제비저표체CD40적내수성DC(Tol-DC).건립소서이위복강심장이식모형.설치이계대조조、미감염DC조급단순만병독감염DC조.관찰각조이식심장존활시간,평정술후7d이식물배척반응、병리분급,병이류식세포술검측수술전후외주혈CD4+ CD25+Treg변화수평.결과 CD40-RNAi만병독재체재체외감염DC 48 h후,CD40 mRNA표체명현수도억제,억제효솔위80.9％.CD40표체명현하강,유74.37％ ±4.08％강지40.07％±4.03％ (P＜0.05).여이계대조조화미감염DC조상비,단순만병독감염DC조이식심장존활시간(14±4)d명현연장(P＜0.01)；술후7d급성배척반응병리분급균명현강저(P＜0.05)；술후3d、7d외주혈CD4+ CD25+ Treg수평균명현승고(P＜0.05).결론 CD4+ CD25+ Treg대수주공자저표체CD40적수돌상세포적소서이식심장구유보호작용.
Objective To explore the effects of CD4+CD25+Treg cell on the allograft after infusion of dendritic cells (DCs) with low expression of CD40 from donor in mouse heart transplantation.Methods In vitro,mouse bone marrow-derived DCs were infected by CD40-RNAi lentiviral vector,and tolerogenic DCs (Tol-DCs) with low expression of CD40 were prepared.A heterotopic abdominal heart transplantation model was established in mice,and the other three groups that were control group,noninfected DC group and lentivirus infected DC group were designed correspondingly.Cardiac allograft survival time was recorded and pathological grading for acute rejection was assessed on the 7 d after heterotopic abdominal heart transplantation.Concentrations of CD4+CD25+Treg cells in peripheral blood were analyzed before and after transplantation by flow cytometry.Results After 48 h infection of DCs by CD40-RNAi lentiviral vector in vitro,the expression of CD40 mRNA was down-regulated significantly,whose inhibition rate was 80.9％.The expression of CD40 was decreased from 74.37％ ±4.08％ to 40.07％ ± 4.03％ (P＜0.05) after 48 h infection.Compared with the control group and the noninfected DC group,the cardiac allograft survival time was significantly prolonged in the CD40-RNAi lentivirus infected DC group,which was (14 ± 4) d(P＜0.01) ; concentrations of CD4+CD25+Treg cells in peripheral blood were increased both on the 3 d and the 7 d after transplantation (P＜0.05) ; the pathological grading for acute rejection was decreased on the 7 d after transplantation (P＜0.05).Conclusion The CD4+CD25+Treg cell in peripheral blood was protective to cardiac allograft in prolonging its survival time in mouse heart transplantation.
