Kovarik J, Koulmanda M, Mandel T E
WHO Collaborating Centre for Vaccinology and Neonatal Immunology, University of Geneva, Switzerland.
Transpl Immunol. 1997 Dec;5(4):307-14. doi: 10.1016/s0966-3274(97)80014-7.
The rejection of discordant foetal pig islet xenografts in nonimmunosuppressed nonobese diabetic (NOD) mice is dominated by polymorphonuclear cell infiltration whereas allografts are almost exclusively infiltrated by mononuclear cells. To determine if this variation is due to different proinflammatory factors generated at the graft site, we analysed graft-site mRNA expression of various cytokines, and the eosinophil attractant chemokine, eotaxin, in a renal subcapsular islet transplant model using organ cultured foetal pig (xenograft) and foetal BALB/c (allograft) pancreas in prediabetic NOD mice. Using semiquantitative RT-PCR on samples recovered at multiple time points during the first 15 post-transplantation days from mice transplanted with either allogeneic or xenogeneic tissue, we found increased expression of IL-2, IL-4. TNF-beta and IL-10 mRNAs at the peak of the cellular infiltrate (on day 5) in both xenografts and allografts but, in contrast to the allografts, no enhanced transcription of IFN-gamma mRNA in the rejecting xenografts. When an allograft and a xenograft were placed at the opposite pole of the same kidney the histological appearance of the rejecting allograft site resembled the xenograft site with significant numbers of eosinophils in both, and enhanced expression of eotaxin and iNOS. Additionally, the xenograft response, unlike the allograft response, was marked by an early increased expression of TNF-alpha and IL-S (day 3) and an almost complete absence of IFN-gamma expression. The results suggest a distinct cell-mediated mechanism for rejection of foetal pancrease xenografts compared to the rejection of foetal pancreas allografts.
在未接受免疫抑制的非肥胖糖尿病（NOD）小鼠中，不匹配的胎猪胰岛异种移植物的排斥反应以多形核细胞浸润为主，而异种移植物几乎完全由单核细胞浸润。为了确定这种差异是否是由于移植部位产生的不同促炎因子所致，我们在糖尿病前期NOD小鼠的肾被膜下胰岛移植模型中，分析了使用器官培养的胎猪（异种移植物）和胎BALB/c（同种移植物）胰腺时，移植部位各种细胞因子以及嗜酸性粒细胞趋化因子（嗜酸性粒细胞趋化蛋白）的mRNA表达。在移植后第15天内的多个时间点，对移植了同种异体或异种组织的小鼠所采集的样本进行半定量逆转录聚合酶链反应（RT-PCR），我们发现在异种移植物和同种移植物中，细胞浸润高峰期（第5天）时白细胞介素-2（IL-2）、白细胞介素-4、肿瘤坏死因子-β（TNF-β）和白细胞介素-10的mRNA表达均增加，但与同种移植物不同的是，在发生排斥反应的异种移植物中，γ干扰素（IFN-γ）mRNA的转录未增强。当将一个同种移植物和一个异种移植物置于同一肾脏的相对两极时，发生排斥反应的同种移植物部位的组织学外观与异种移植物部位相似，两者均有大量嗜酸性粒细胞，且嗜酸性粒细胞趋化蛋白和诱导型一氧化氮合酶（iNOS）的表达增强。此外，与同种移植物反应不同，异种移植物反应的特点是肿瘤坏死因子-α（TNF-α）和白细胞介素-6（IL-6）早期表达增加（第3天），且几乎完全没有IFN-γ表达。结果表明，与胎胰腺同种移植物的排斥反应相比，胎胰腺异种移植物的排斥反应存在独特的细胞介导机制。
