The effects of pretreatment with donor antigen and immunosuppressive agents on fully allogenic tracheal graft

Abstract

Obliterative bronchiolitis is a major clinical problem in cases involving a transplanted lung. We examined drug-induced tolerance to a fully allogenic tracheal graft in a murine heterotopic transplantation model. Recipient mice (C57BL/6) were primed iv with 1 x 10(8) splenocytes of donor mice (BALB/c). Day 0 was the day of the splenocyte injection. Cyclophosphamide and Busulfan were injected intraperitoneally on day 2. On day 3, 1 x 10(7) donor bone marrow cells were intravenously injected. On day 28, a donor tracheal graft was implanted into a subcutaneous pocket. Grafts were harvested at 3-week intervals, and the degree of obstruction of the inner cavity, the condition of epithelium, and the viability of chondrocytes were examined. All of the isograft controls (BALB/c) and grafts implanted in the T cell-free recipients (BALB/c-nu) showed patent, lined epithelium and viable chondrocytes. All allografts tested showed total luminal occlusion by granulative tissue and inflammatory cells, and the epithelium was totally absent. Five of 11 drug-treated grafts were completely patent, although the epithelium was almost absent and the chondrocytes were substantially destroyed. However, when the chimerism was analyzed by flow cytometry analysis of the recipient T cells, approximately 90% of the donor cells were recognized. Even by this pre-treatment-induced chimerism, a transplanted allogenic trachea was not completely preserved. The present results suggest that a non-allogenic response might have contributed to the rejection.