摘要
目的研究重组腺病毒AdCD40Ig联合供体静息B淋巴细胞预处理策略在小鼠诱导建立特异性移植耐受,延长后续进入的供体来源皮肤移植物存活时间的作用。方法设定空白对照(1组)和第三方空白对照(2组),以AdCD40Ig(3组)、C57BL/6静息B细胞(4组)、AdCD40Ig联合供体静息B细胞(5组)及第三方实验对照(6组)等不同组合在皮肤移植前1周预先处理受体BALB/c小鼠,观察皮肤移植物存活情况。双抗夹心法ELISA测定AdCD40Ig处理后小鼠血清CD40Ig水平。结果经小鼠尾静脉注入AdCD40Ig1×109efu后,于第7天血清CD40Ig水平可达130.6±11.2μg/ml的峰值,第8周后血清CD40Ig内仍有一定水平。皮肤移植实验结果各组MST(d)分别为10.33±0.46、9.83±0.53、10.83±0.25、10.00±3.24、63.50±10.45和11.50±3.39。统计处理显示第5组皮肤移植物MST明显延长,与第3组、第4组和第6组相比具有显著性差异(P<0.01);而第1组、第2组、第3组、第4组之间无显著性差异。表明仅有AdCD40Ig联合供体静息B细胞预处理可以观察到供体特异性的皮肤移植物长期存活现象。单独使用静息淋巴细胞预处理或者AdCD40Ig,均不能延长皮肤移植物存活时间。结论AdCD40Ig联合供体静息B细胞预处理策略能在小鼠皮肤移植模型中显著延长后续进入的供体来源皮肤移植物存活时间,是一种具有临床应用前景而值得深入研究的免疫耐受诱导策略。
Objective: To investigate the efficacy of recombinant adenovirus AdCD40Ig with donor resting B lymphocytes pretreatment in prolonging the survival time of murine skin graft and in inducing the establishment of donor - specific transplant tolerance.Methods: The animals were allocated into the following groups: control (group 1), third - partner control (group 2), AdCD40Ig (group 3), C57BL/6 resting B lymphocytes (group 4), AdCD40Ig with mesting B lymphocytes (group 5) and third - partner experimental (group 6) ; mice was treated 1 week prior to skin transplantation; the survival of graft was monitored closely and the CD40Ig in the recipients was detected via EKSA. Results: Seven days after AdCD40Ig was injected via tail veins of mice, senun CIMOIg peaked at 130± 11.2μg/ml and remained elevated in 8 weeks. Mean survival times (days) of all six groups were 10.33 ± 0.46, 9.83±0. 53, 10.83 ± 0.25, 10.00 ± 3.24, 63.50 ± 10.45 and 11.50 ± 3.39 respectively, Survival time of skin graft in group 5 is significantly prolonged compared with that in the other five groups ( P 〈 0.01 ) ; the differences between other pretreatments and their controls were not significant, indicating Recombinant adenovirus AdCIMOIg with donor resting B lymphocytes pretreatment could improve the survival of skin graft. Recombinant adenovirus AdCD40Ig or donor resting B lymphocytes pretreatment alone had no detectable effect. Conclusion: The pretreatment strategy adopted in this experiment- recombinant adenovirus AdCD4OIg with donor resting B lymphocytes - could significantly improve the survival of donor - specific skin grafts, suggesting that this strategy could induce the establishment of specific transplant tolerance and possibly be applied in clinical setting and worth further study.
出处
《华西医学》
CAS
2006年第2期319-321,共3页
West China Medical Journal
基金
四川省科技厅基金资助项目(03JY029-075-1)。