Characterization of allograft rejection in an experimental model of small intestinal transplantation.
Characterization of allograft rejection in an experimental model of small intestinal transplantation.
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DOI：
10.1016/s1091-255x(98)80071-1
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发表时间：
1998-07-01
期刊：
影响因子：
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通讯作者：
Esquivel, C O
中科院分区：
文献类型：
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作者：
Hayashi, M;Martinez, O M;Esquivel, C O
移植物排斥反应仍然是临床小肠移植成功的主要障碍。本研究的目的是在小肠移植实验模型中描述同种异体排斥反应的组织病理学和免疫学参数。在同种异体和同基因大鼠品系组合中进行异位肠移植。另一组同种异体受体从移植后第1天开始接受他克莫司（1 mg/kg/天）治疗7天。同种异体移植物和同种异体移植物的受体在移植后1至7天被杀死，并且他克莫司处理的同种异体移植物受体在第4天和第7天被杀死。对移植物和天然肠进行组织病理学和细胞因子基因表达检查。在移植后第3天观察到非常早期的排斥反应，在第7天出现严重排斥反应。急性移植物排斥反应的关键组织病理学特征，包括细胞凋亡、隐窝上皮细胞损伤和炎性浸润，在第4天一致可识别，并在严重程度上进展至第7天。在第1 - 7天，在同种异体移植物中容易检测到白细胞介素（IL）-2，IL-4，IL-5，IL-6，干扰素-γ（IFN-γ）和肿瘤坏死因子-α mRNA。然而，只有IFN-γ mRNA表现出显着的早期和持续增加，在同种异体移植物相比，同种异体移植物和天然肠。用他克莫司治疗同种异体移植受者可消除排斥反应的主要组织病理学特征，并显著抑制IFN-γ基因表达。这些结果表明，小肠移植中的移植物排斥的特征在于由IFN-γ产生标记的局部和特异性免疫应答，其导致隐窝上皮细胞损伤和凋亡。他克莫司可消除与IFN-γ基因表达显著抑制相关的排斥反应的组织病理学特征。
Graft rejection continues to be a major barrier to the success of clinical small intestinal transplantation. The objective of this study was to characterize histopathologic and immune parameters of allograft rejection in an experimental model of small intestinal transplantation. Heterotopic intestinal transplants were performed in allogeneic and isogeneic rat strain combinations. An additional group of allogeneic recipients was treated with tacrolimus (1 mg/kg/day) for 7 days beginning on posttransplant day 1. Recipients of allografts and isografts were killed on days 1 to 7 following transplantation, and tacrolimus-treated allograft recipients were killed on days 4 and 7. Grafts and native intestines were examined for histopathology and cytokine gene expression. Very early rejection was observed on posttransplant day 3 and severe rejection was apparent by day 7. The key histopathologic features of acute graft rejection including apoptosis, crypt epithelial cell injury, and an inflammatory infiltrate were uniformly identifiable on day 4 and progressed in severity through day 7. Interleukin (IL)-2, IL-4, IL-5, IL-6, interferon-gamma (IFN-gamma), and tumor necrosis factor-alpha mRNA were readily detectable in allografts on days 1 to 7. However, only IFN-gamma mRNA showed a significant early and sustained increase in allografts as compared to isografts and native intestine. Treatment of allograft recipients with tacrolimus abrogated the major histopathologic features of rejection and markedly inhibited IFN-gamma gene expression. These results indicate that graft rejection in small intestinal transplantation is characterized by a local and specific immune response marked by IFN-gamma production that results in crypt epithelial cell injury and apoptosis. Tacrolimus abrogates the histopathologic features of rejection in association with a marked inhibition of IFN-gamma gene expression.