肺在急性移植物抗宿主病模型中的相对免疫豁免

Relative tolerance of lung in murine model of acute graft-versus-host disease

目的探讨肺在急性移植物抗宿主病（aGvHD）模型中是否存在免疫豁免及其可能机制。方法实验以C57BL／6小鼠为供者，以C57BL／6小鼠与DBA／2小鼠杂交F1代的B6D2F1小鼠为受者建立aGVHD模型（半相合移植组，移植物中的脾细胞与骨髓细胞之比为2：1）；以BALB／c小鼠为受者建立aGVHD模型，移植物中的脾细胞与骨髓细胞之比分别为2：1（MHC不合1组）和4：1（MHC不合2组）；另设以C57BL／6小鼠为受者的同系移植组（移植物中的脾细胞与骨髓细胞之比为2：1）。移植后观察受鼠的aGVHD评分、存活时间以及肝、皮肤、小肠和肺组织的病理改变及其7干扰素（IFN-γ）的含量。结果半相合移植组受鼠的42d存活率为20％，第28天出现典型的aGVHD表现和组织损伤，但肺组织的损伤明显较经典器官轻；而MHC不合1组和2组出现严重的aGVHD，第12天小鼠多数死亡，其中MHC不合2组出现严重的间质性肺炎。半相合移植组小鼠的肺组织中IFN-γ含量明显高于皮肤、肝和小肠中的IFN-γ含量（P〈0．05）。结论肺在小鼠aGVHD模型中存在相对免疫豁免，它与供受者间主要组织相容性复合物的相合程度以及肺组织中IFN-γ水平相关。

Objective To analyze the immune privilege of lung in acute graft-versus-host disease （aGVHD）. Methods The models of aGVHD were established, and C57BL/6J→C57BL/6J model was used as control. The clinical scores and survival were observed. The pathological injuries were compared between the lung and traditional target organs （liver, small intestines and skin）. The expression of IFN-γ in different organs after transplantation was detected by ELISA. Results Allogeneic hematopoietic stern cell transplantation （HSCT） mice had high 42-day survival rate （20%） post-transplantation, and recipients of allogeneic grafts showed classical symptoms and histological injury, and pathological changes of lung were not as serious as the liver, small intestine, skin at day 28 after transplantation. Syngeneic mice all survived at day 42 after transplantation, without GVHD symptoms and pathological changes. The mice in MHC-disparate mice （2 ： 1 and 4 ： 1 groups） died significantly faster at a median of 12 days after transplantation, with severe changes of clinical symptoms and pathology of classical organs, and MHC-disparate mice （4：1 groups） had developed severe interstitial pneumonitis. The mean IFN-γ concentration in the lung of allogeneic HSCT mice was obviously increased in the first and second week after transplantation, the IFN-γ concentrations of target organs （liver, small intestines, skin） were slightly increased in the first and second week after transplantation, and there were statistically significant difference from lung （P〈0. 05）. Conclusion There wasrelativeimmune privilege of lung in a murine model of aGVHD induced by HSCT, which was associated with the expression of MHCin the mice and IFN-gamma of lungs after transplantation.