Ikonen T S, Brazelton T R, Berry G J, Shorthouse R S, Morris R E
Transplantation Immunology, Department of Cardiothoracic Surgery, Stanford University School of Medicine, CA 94305-5407, USA.
Transplantation. 2000 Sep 27;70(6):857-63. doi: 10.1097/00007890-200009270-00002.
Because epithelial cells are targets of alloimmune injury leading ultimately to airway obliteration, we tested whether epithelial re-growth could prevent obliterative airway disease (OAD) in orthotopic tracheal allografts.
Brown Norway tracheal segments were orthotopically transplanted into nonimmunosuppressed Lewis rats. Allografts were removed on days 2-10 (n=13), 30 (n=4), and 60 (n=5) for histology, computerized morphometry (obliteration), and immunohistochemical detection of mononuclear cells, smooth muscle alpha-actin, and tissue phenotype. Normal tracheas, host tracheas, and heterotopically transplanted allografts served as controls.
Orthotopic allografts removed on days 2-10 exhibited epithelial damage and re-growth and mononuclear cell infiltration. On days 30 and 60, partially ciliated cuboidal or attenuated epithelium completely covered the lumen. Although mononuclear cells declined, numerous T cells with a high CD4/CD8 ratio were found in the epithelium till day 60. Orthotopic allograft epithelium expressed donor phenotype on day 7, but recipient phenotype on days 30 and 60. Despite subepithelial alpha-actin positive myofibroblast proliferation, obliteration did not progress from day 7 to 30 and 60 (35, 30, and 33%, respectively). Although more than in normal or host tracheas, the obliteration in orthotopic allografts on days 30 and 60 was significantly less (P<0.001) than in heterotopic allografts.
We describe, for the first time, longterm patency of fully histoincompatible orthotopic tracheal allografts in nonimmunosuppressed rats. Despite acute alloimmune injury and induction of myofibroblast proliferation, epithelial re-growth from the host limited the progression of OAD, thus emphasizing the role of epithelium in the control of airway obliteration.
由于上皮细胞是同种异体免疫损伤的靶细胞，最终导致气道闭塞，我们测试了上皮再生是否可以预防原位气管同种异体移植中的闭塞性气道疾病（OAD）。
将棕色挪威大鼠的气管段原位移植到未免疫抑制的Lewis大鼠体内。在第2 - 10天（n = 13）、30天（n = 4）和60天（n = 5）取出同种异体移植物，进行组织学检查、计算机形态计量学（闭塞情况）以及单核细胞、平滑肌α - 肌动蛋白和组织表型的免疫组化检测。正常气管、宿主气管和异位移植的同种异体移植物作为对照。
在第2 - 10天取出的原位同种异体移植物表现出上皮损伤、再生以及单核细胞浸润。在第30天和60天，部分有纤毛的立方上皮或变薄的上皮完全覆盖管腔。尽管单核细胞数量减少，但直到第60天，上皮中仍发现大量CD4/CD8比值高的T细胞。原位同种异体移植物上皮在第7天表达供体表型，但在第30天和60天表达受体表型。尽管上皮下α - 肌动蛋白阳性肌成纤维细胞增殖，但从第7天到30天和60天闭塞并未进展（分别为35%、30%和33%）。尽管原位同种异体移植物在第30天和60天的闭塞程度比正常或宿主气管更严重，但明显低于异位同种异体移植物（P < 0.001）。
我们首次描述了在未免疫抑制的大鼠中，完全组织不相容的原位气管同种异体移植物的长期通畅情况。尽管存在急性同种异体免疫损伤并诱导肌成纤维细胞增殖，但宿主上皮的再生限制了OAD的进展，从而强调了上皮在控制气道闭塞中的作用。
