The establishment of chronic lung rejection model using rat left lung allotransplantation

（目的）为促进肺移植（LTx）后闭塞性细支气管炎（OB）综合征的实验研究，本研究拟建立大鼠慢性肺排斥反应模型。（实验）将左肺移植物原位移植在胸腔中，WKAH-至-F344作为同种异体移植模型。所有大鼠接受CsA溶解在橄榄油中，以25 mg/kg体重的剂量肌肉注射，直到LTx后14天。此后，他们没有任何免疫抑制，直到16周后Ltx。移植肺组织学检查均发现OB。这可能是因为大鼠在移植后短期免疫抑制容易诱导免疫耐受（同种异体LTx的永久移植物接受），因此在停止免疫抑制后大鼠没有发生急性肺排斥反应。因此，我们研究了注射rIL-2是否会在环孢素A免疫耐受的移植大鼠中引起急性排斥反应。为了简化实验模型，我们采用大网膜异位气管移植，以BN-to-LEW作为同种异体移植模型。I组（未使用免疫抑制剂）移植后4周出现气管移植物气道阻塞。Ⅱ组（移植后第2、3天注射环孢素A 25 mg/kg）气管腔通畅，气道上皮正常。第三组（第二组注射rIL-2），IL-2剂量依赖性地致气管移植物气道阻塞，直至40，000 IU/d，持续10 d。结果提示，同种异体气管移植后气道阻塞可能与免疫反应有关，rIL-2可逆转环孢素A引起的大鼠同种异体气管移植免疫耐受。因此，在环孢素A免疫耐受的情况下，Ltx后注射rIL-2可诱导肺移植大鼠发生急性排斥反应，导致移植肺发生OB。

(PURPOSE) To promote the experiment work on obliterative bronchiolitis (OB) syndrome following lung transplantation (LTx), we planed to establish the chronic lung rejection model using rats. (EXPERIMENTS) Left lung grafts will be orthotopically transplanted in the thorax, WKAH-to-F344 as allotransplanted model. All rats receive CsA dissolved in olive oil intramuscularly in a dosage of 25mg/kg body weight until day 14 after LTx. Thereafter they did not any immunosuppression until week 16 after Ltx. They had any histological finding of OB in transplanted lung. This may be explained by the fact that rat had no acute lung rejection followed by the discontinuation of immunosuppression, because rats are easily induced to be imunological tolerant (permanent graft acceptance of the allogenic LTx) by short term immunosuppression after trasplantation. Therefore, we examined whether rIL-2 injection may induce acute rejection in transplanted rat under immunological tolerance due to cyclosporine A or not. To simplify the experimental model, we used heterotopical tracheal transplantation into omentum, using BN-to-LEW as allotransplanted model. Group I (no immunosuppression) had airway obstruction of tracheal allografts at 4 weeks after transplantation. Group II (received cyclosporine A 25mg/kg injection at days 2 and 3 after transplantation) had patency of tracheal lumen and normal airway epithelium. Group III (received rIL-2 injection in Group II) showed airway obstruction of tracheal allograft in IL-2 dose-dependent fashion until 40,000 IU/day for 10days. These results show that airway obstruction of tracheal allografts may be related to immunological reaction, and rIL-2 could reverse immunological tolerance due to cyclosporine A in rat allotransplantation. Therefore rIL-2 injection might induce acute rejection to lung-transplanted rat under immunological tolerance due to cyclosporine A injection after Ltx and cause OB on trasplanted lung.