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The inhibitory effect of donor-derived DCs highly expressing functional indoleamine 2,3-dioxygenase on acute rejection in mice small bowel transplantation
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- Author:
- No author available
- Journal Title:
- CHINESE JOURNAL OF ORGAN TRANSPLANTATION
- Issue:
- 2
- DOI:
- 10.3760/cma.j.issn.0254-1785.2007.02.003
- Key Word:
- 双加氧酶类;树突细胞;小肠移植;移植物排斥;小鼠
Abstract： 目的 观察干扰素γ(IFN-γ)诱导供者(C57BL/6小鼠)脾树突细胞(DC)表达吲哚胺2,3双加氧酶(IDO)的情况;研究受者(BalB/c小鼠)小肠移植术前输注高表达IDO的供者DC对排斥反应的抑制作用.方法 用IFN-γ诱导供者DC表达IDO;半定量逆转录聚合酶链反应、免疫印迹法及毛细管电泳法检测IDO表达水平及活性,混合淋巴细胞培养(MLR)测定IDO刺激T细胞增殖的能力.利用小鼠异位小肠移植模型,设单纯移植组、DC输注移植组(术前输注供者脾DC 2×106个)及诱导DC输注移植组(术前输注经IFN-γ诱导的供者脾DC 2×106个),术后观察移植肠存活时间并行病理学检查.结果 经IFN-γ诱导的脾DC IDO分子mRNA转录水平(相对量)、IDO蛋白表达水平(相对量)及培养液中犬尿氨酸浓度分别为(1.23±0.02)、(2.74±0.01)以及(76.52±0.44)μmol/L,未经IFN-γ诱导的脾DC分别为(1.05±0.05)、(1.40±0.17)及(43.31±0.48)μmol/L,前者显著增强(P＜0.01).脾DC对同种T细胞增殖的刺激作用在IFN-γ诱导后减弱,在加入IDO的特异性抑制剂后增强.输注诱导DC移植组移植肠中位存活时间(12 d)较单纯移植组(6 d)及输注DC移植组(7.5 d)显著延长(P＜0.01),而移植肠病理分级显著性降低(P＜0.05).结论 IFN-γ可诱导小鼠脾DC高表达活性的IDO,后者可减弱DC刺激T细胞增殖的能力.受者术前输注高表达IDO的供者DC能够诱导针对供者的特异性免疫耐受而减轻排斥反应.
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