与C3H相比,BALB/c受体DBA/2小鼠角膜移植可显著延缓移植排斥反应,促进基因转移研究

R. Ignatius, E. Zhang, Felix Schulte, M. Schroff, U. Rüschendorf, A. Müller, B. Wittig, F. Hoffmann
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引用次数: 0

摘要

为了研究基因转移对实验性角膜移植的影响,移植物应该可靠地排斥,但要经过一段时间,这允许多种干预。我们感兴趣的是通过供体和受体动物的mhc匹配来延迟移植存活时间,并省略局部地塞米松治疗,这是费力的,可能会干扰给药DNA的表达。与C3H (H-2k)相比,BALB/c (H-2d)受体对DBA/2 (H-2d)角膜的排斥反应发生明显延迟(25.0±5.6 vs 14.5±4.1天,p=0.038),并与引流淋巴结中异体特异性T细胞增殖表达和IFN-分泌有关。受体下眼睑IL-4/CTLA-4 DNA MIDGE TM载体基因枪处理可显著延长BALB/c小鼠DBA/2角膜的生存期。这种改进的和不含地塞米松的方案可能有利于开发新的治疗策略,例如角膜移植中的局部基因转移。
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Transplantation of DBA/2 Mouse Corneas in BALB/c Recipients SignificantlyDelays Graft Rejection Compared with C3H Grafts and FacilitatesStudies on Gene Transfer
To study the impact of gene transfer in experimental corneal transplantation, grafts should reliably be rejected but after a time span, which allows multiple interventions. We were interested in delaying transplant survival time through MHC-matching of donor and recipient animals and in omitting local dexamethasone treatment, which is laborious and could potentially interfere with the expression of administered DNA. Rejection of DBA/2 (H-2d) corneas by BALB/c (H- 2d) recipients occurred significantly delayed compared with C3H (H-2k) grafts (25.0 ± 5.6 vs. 14.5 ± 4.1 days, p=0.038), and correlated with the expression of allospecific T cell-proliferation and IFN- secretion in draining lymph nodes. Gene gun treatment with IL-4/CTLA-4 DNA MIDGE TM vectors in the lower lid of recipients significantly prolonged survival of DBA/2 corneas in BALB/c mice. This refined and dexamethasone-free protocol may be advantageous for the develop- ment of novel treatment strategies, e.g., local gene transfer, in corneal transplantation.
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