负载Ad-CTLA4Ig的未成熟树突状细胞延长大鼠移植肾存活时间的探讨

目的 探讨负载细胞毒性淋巴细胞抗原4免疫球蛋白基因重组腺病毒(Ad-CTLA4Ig)的受者未成熟树突状细胞(DC)对大鼠移植肾存活时间的影响.方法 选择雄性SD大鼠为供者,雄性Wistar大鼠为受者,建立大鼠肾移植模型.将受者随机分为4组,每组12只.制备Ad-CTLA4Ig及受者未成熟DC悬液,37℃混合孵育6 h,于移植前7 d,实验组经腹腔内注射负载Ad-CTLA4Ig的DC悬液;Ad-CTLA4Ig对照组、重组腺病毒空载体(Ad-VG)对照组和生理盐水(NS)对照组分别经腹腔内注射1 ml Ad-CTLA4Ig、Ad-VG和NS.观察各组移植肾的存活时间、组织形态学改变、受者血液中腺病毒中和抗体滴度、血清CTLA4Ig水平及混合淋巴细胞反应(MLR)的变化.结果 实验组移植肾存活时间为(94.6±9.0)d,较各对照组显著延长:Ad-CTLA4Ig对照组为(39.6±10.6)d,Ad-VG对照组为(8.6±2.8)d,NS对照组为(8.4±2.6)d],差异均有统计学意义(P＜0.01),实验组移植肾组织损伤程度较轻,血液中腺病毒中和抗体滴度及混合淋巴细胞反应指数均较各对照组显著减少;实验组血清CTLA4Ig水平较Ad-CTFLA4Ig对照组显著升高.结论 负载Ad-CTLA4Ig的受者未成熟DC可减少腺病毒中和抗体,维持CTLA4Ig的稳定表达,从而延长大鼠移植肾的存活时间.

Prolongation of survival time of rats renal allografts by immature dendritic cells loading recombinant adenoviral CTLA4Ig

Objective To explore the influence of immature dendritic cells(DC) from recipients loading recombinant adenoviral cytotoxic T lymphocyte antigen 4 immuglobin(Ad-CTLA4Ig) on the survival of rats'renal allografts. Methods Rat kidney transplantation models were established using male SD rats as donors and male Wistar rats as recipients. Recipients were divided into four groups(n =12). Ad-CTLA4Ig and recipients' immature DC were prepared and co-incubated in thirty-seven centigrade for six hours. These DC loading Ad-CTLA4Ig were injected into the recipients by intraperitoneal seven days before transplantation. Ad-CTLA4Ig,recombinant adenoviral vacuous tragers (AdVG) and normal saline (NS) were injected respectively by same way into each control group respectively. The survival time of renal allografts, morphologic impairment index, Serum CTLA4Ig and adenovirucidin titer and mixed lymphocyte reaction (MLR) were detected. Results The survival time of renal allografts were remarkably longer than those of control groups, Morphologic impairments index, adenovirucidin titer and the stimulation index of MLR were markably lower than those of control groups. Serum CTLA4Ig was remarkably higher than those of Ad-CTLA4Ig group. Conclusion Immature DC from recipients loading Ad-CTI.A4Ig can reduce adenovirucidin, induce stable immunotolerance, keep stable serum CTLA4Ig and prolong the survival time of rat renal allografts.