Latner Thoracic Surgery Research Laboratories, Toronto General Research Institute, University Health Network, University of Toronto, Toronto, Ontario, Canada.
Transplantation. 2012 Jun 27;93(12):1212-20. doi: 10.1097/TP.0b013e318250fbf5.
Obliterative bronchiolitis after lung transplantation is associated with intrapulmonary lymphoid neogenesis. The purpose of this study was to examine the role of lymphoid neogenesis, especially its relationship with secondary lymphoid organs (SLOs) in allograft airway rejection.
A murine intrapulmonary tracheal transplant model and a conventional subcutaneous tracheal transplant model were tested using wild-type control mice and splenectomized lymphotoxin α knockout (LT) mice deficient in SLOs as recipients.
In both subcutaneous and intrapulmonary tracheal transplant models using wild-type animals, tracheal isografts remained open without rejection, whereas allografts showed progressive luminal obliteration after transplantation. Lymphoid neogenesis containing alloreactive T cells was observed in the lungs, which received an intrapulmonary tracheal allograft. Despite a lack of SLOs, intrapulmonary allografts in splenectomized LT mice were rejected and obliterated by day 28, but the rejection of subcutaneous allografts was significantly delayed. Extensive lymphoid neogenesis was observed in the lungs of both intrapulmonary and subcutaneous allograft LT recipients. Increased proliferation of CD4 T cells and B220 B cells was observed in the lungs but not in the thymus or bone marrow.
Intrapulmonary lymphoid neogenesis is capable of mounting alloimmune responses without SLOs. Tracheal allograft rejection occurs as efficiently as in wild-type animals when it is placed in the lungs. Tracheal allograft rejection in the subcutaneous tissue occurs in a delayed manner without SLO in association with intrapulmonary lymphoid neogenesis.
肺移植后闭塞性细支气管炎与肺内淋巴组织生成有关。本研究旨在探讨淋巴组织生成，尤其是其与同种异体移植物气道排斥反应中的次级淋巴器官（SLO）的关系。
采用野生型对照小鼠和脾切除淋巴毒素α 敲除（LT）小鼠作为受体，分别进行肺内气管移植模型和传统皮下气管移植模型的实验。
在使用野生型动物的皮下和肺内气管移植模型中，气管同种移植物保持通畅，无排斥反应，而同种异体移植物在移植后出现进行性管腔闭塞。在接受肺内气管同种异体移植物的肺部观察到含有同种反应性 T 细胞的淋巴组织生成。尽管缺乏 SLO，但脾切除 LT 小鼠的肺内同种异体移植物在第 28 天被排斥和闭塞，但皮下同种异体移植物的排斥明显延迟。在肺内和皮下同种异体移植物 LT 受者的肺部均观察到广泛的淋巴组织生成。在肺部而非胸腺或骨髓中观察到 CD4 T 细胞和 B220 B 细胞的增殖增加。
肺内淋巴组织生成能够在没有 SLO 的情况下引发同种免疫反应。当气管同种异体移植物放置在肺部时，与野生型动物一样有效地发生排斥反应。在没有 SLO 的情况下，与肺内淋巴组织生成相关的皮下组织气管同种异体移植物排斥反应发生延迟。
