Basic Research of Heart Lung Transplantation

本项目采用日本猕猴单肺移植模型，研究了同种和异种肺移植的免疫应答。(1)无免疫抑制的同种异体肺移植猴在7天内胸片显示实变，镜下检查显示同种异体肺移植排斥。FK506免疫抑制的猴子存活5 ~ 182天，在动物死亡或牺牲时，7只同种异体移植物中有6只被认为是功能正常的。FK506被认为是一种有效的肺同种异体移植免疫抑制剂。(2)探讨胸腔灌洗液（PLF）诊断肺同种异体和异种移植排斥反应的可行性。PLF淋巴细胞亚群的变化与外周血淋巴细胞亚群的变化无关，并且随着移植肺的排斥反应，PLF淋巴细胞CD4+/CD8+比值降低。(3)免疫荧光染色法检测同种异体移植肺。即使在临床上足够的免疫抑制下，MHC 1类和2类抗原的表达也能被识别。同种异体移植物中的CD4（+）细胞、CD8（+）细胞和CD20（+）细胞被认为在同种异体移植物排斥反应中起重要作用。

Immunological response to allo- and xeno-lung graft was studied in this project using single lung transplantation model with Japanese Macaque monkeys. (1) Monkeys with lung allograft without immunosuppression showed consolidation by chest roentgenogram within 7 days and microscopic examination revealed rejected allograft. Monkeys with FK506 immunosuppression survived from 5 to 182 days and 6 allograft out of seven were considered to be functioning at the time of animal death or sacrifice. FK506 was considered as effective immunosuppressant for allotransplantation of the lung. (2) The feasibility of pleural lavage fluid(PLF) for the diagnosis of pulmonary allo- and xenograft rejection was studied. The change of lymphocyte subsets in PLF was independent from that in peripheral blood, and that CD4+/CD8+ ratio of lymphocytes in PLF decreased as the grafted lung was rejected. (3) Allografted lungs were examined with immunofluorescent staining methods. The expression of the MHC class 1 and 2 antigens were recognized even under clinically sufficient immunosuppression. CD4(+) cells, CD8(+) cells, and CD20(+) cells in the allograft was considered to play important role in the allograft rejection.