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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 characterized the morphological changes and infiltrating cells in the transplanted hearts. Graft 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 periphery. These cells stained positive for rat MHC class II antigens, the ED1-macrophage marker and the CD4 antigen, and were thus considered to be macrophages. In comparison, grafts harvested at day 56 had signs of interstitial fibrosis and some arteries showed pronounced intimal thickening. There was a moderate infiltrate of cells both in the peripheral and central parts of the graft, consisting mainly of MHC class II+/ CD4+/ED1+ macrophages. Very few T cells and NK cells were noticed. Termination of DSG after 28 days does not trigger a humoral rejection. However, the grafts exhibit morphological changes equivalent to those seen in chronic allograft rejection. In addition, the characteristics of the infiltrating cells conformed with cellular infiltrates associated with chronic allograft rejection. Hence, this model could in the future prove to be useful for studies of mechanisms involved in chronic xenograft rejection.

In two kidney transplant patients, one of whom had panel-reactive antibodies (PRA) before transplantation, a pretransplant negative donor-recipient crossmatch became positive within the 1st week after transplantation. Simultaneously, good graft function deteriorated to a state of anuria. One patient graft biopsy showed a vascular rejection, whilst the other patient biopsy was unrevealing. Both patients were treated with plasmapheresis and a new immunosuppressive drug, 15-deoxyspergualin (DSG). Plasmapheresis was performed for 6 and 9 days, respectively, and DSG was given for 5 days in a dosage of 6 mg/kg body weight per day. One of the patients received methylprednisolone i.v. in addition. During treatment the cross-match became negative and has since remained that way. In both patients the graft function was restored. No adverse effects were seen from the treatment, except for a slight leukocytopenia and thrombocytopenia.

The aim of the present investigation was to study the possible synergistic effect between cyclosporin A (CsA) and antithymocyte globulin (ATG), using the potent immunostimulator, Linomide. DA rats were transplanted with a PVG/c heart to the neck vessels, and the recipients were treated for 10 days with oral CsA (10mg/kg), oral Linomide (160mg/kg) and/or ATG, which was given as a single dose of either 0.02 ml, 0.1 ml or 0.2 ml prior to transplantation. Rats given a combination of ATG and Linomide or CsA and Linomide were used as controls. Synergism between CsA and ATG was tested using the two immunosuppressive drugs given in combination in order to override the challenge of Linomide. CsA or ATG treatment alone resulted in rats with long-term surviving grafts. Addition of Linomide to CsA-treated recipients was followed by early graft rejection. Similarily, Linomide triggered rejection in rats given a low dose of ATG and in recipients given a high dose of ATG if Linomide treatment was prolonged to 21 days. The combination of ATG, CsA and 21 days of Linomide resulted in a significantly prolonged graft survival compared with either ATG + Linomide or CsA + Linomide. These findings demonstrate the synergistic capacity of ATG and CsA in combined immunosuppressive therapy.