Mixed chimera ラットによる同種肺移植における移植片生着延長効果に関する検討

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Lung transplantation is now routinely performed for a wide range of end-stage cardiopulmonary disorders. However, chronic rejection and adverse effects of long-term immunosuppressive pharmacotherapy, including infections, metabolic abnormalities and malignancy, still remain severe problems. Induction of donor-specific tolerance has been suggested as one potential approach to overcome this limitation. The purpose of this study is to investigate whether long-term acceptance of lung allografts can be achieved by induction of mixed chimerism. We established mixed chimera rats by transplantation of a mixture of T-cell depleted (TCD) syngenic and TCD allogenic ACI bone marrow cells into myeloablated F344 recipients which had been administered cyclophosphamide on day -3, -2, -1 and busulfan on day -1 and been whole body lethally irradiated on day 0. Twenty-four percent of the animals which underwent this procedure were engrafted with a level of peripheral blood lymphcyte chimerism ranging between 17% and 87% four weeks after bone marrow transplantation. Using a cuff technique, left lung transplantation was performed to the mixed chimera rats five weeks after bone marrow transplantation. Donor-strain ACI lung allografts were accepted for more than 100 days without evidence of acute rejection. However, airway changes, peribronchial lymphocyte infiltration and expression of MHC class II antigen locally on the bronchial epthelium, were found histologically on the ACI lung allografts 120 days after transplantation. These histological changes were thought to represent chronic rejection. These results indicate that induction of mixed chimerism in our protocol has the potential to achieve long-term acceptance of major histocompatibility complex-mismached lung allografts in rats. However, airway changes thought to represent chronic rejection could not be avoided.
札幌医科大学の論文
1997-12-01

Mixed chimera ラットによる同種肺移植における移植片生着延長効果に関する検討

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