A MORPHOLOGICAL SEQUENTIAL STUDY OF MOUSE-TO-RAT CARDIAC XENOGRAFTS

Long-term survival of a concordant xenograft can be achieved by using cyclosporine (CyA) and deoxyspergualin (DSG) for immunosuppression. We have demonstrated in a mouse-to-rat heterotopic heart transplantation model that DSG treatment can be stopped after 4 weeks with the grafts remaining beating. In this investigation we have sequentially charact erized the morphological changes and infiltrating cells in the transpl anted hearts. Craft recipients were killed 9 days, 28 days and 56 days after transplantation. At days 9 and 28, the grafts exhibited a well- preserved morphology, with infiltrating cells restricted only to the p eriphery. These cells stained positive for rat MHC class II antigens, the ED1-macrophage marker and the CD4 antigen, and were thus considere d to be macrophages. In comparison, grafts harvested at day 56 had sig ns of interstitial fibrosis and some arteries showed pronounced intima l thickening. There was a moderate infiltrate of cells both in the per ipheral and central parts of the graft, consisting mainly of MHC class II+/CD4(+)/ED1(+) macrophages. Very few T cells and NK cells were not iced. Termination of DSG after 28 days does not trigger a humoral reje ction. However, the grafts exhibit morphological changes equivalent to those seen in chronic allograft rejection. In addition, the character istics of the infiltrating cells conformed with cellular infiltrates a ssociated with chronic allograft rejection. Hence, this model could in the future prove to be useful for studies of mechanisms involved in c hronic xenograft rejection.