ANTI-CD4 MONOCLONAL-ANTIBODY TREATMENT IN COMBINATION WITH TOTAL LYMPHOID IRRADIATION AND CYCLOSPORINE-A IN HAMSTER-TO-RAT CARDIAC TRANSPLANTATION

Significantly prolonged graft survival (GS) of hamster hearts transpla nted heterotopically into rats can be achieved by different immunosupp ressive treatment strategies. The exact mechanism of graft rejection i s unclear, but it seems to be a primarily humoral, antibody-mediated t ype of rejection. The histopathology of long-term surviving grafts is controversial and the morphology of lymphoid tissue in spleens and lym ph nodes as the possible site of anti-donor antibody formation has not previously been investigated. This report demonstrates a significantl y prolonged GS in hamster-to-rat cardiac transplantation after combine d treatment with total lymphoid irradiation (TLI), cyclosporin A (CyA) and anti-CD4 monoclonal antibodies (MAb), where long-term GS (>100 da ys) could be achieved in a few animals. The histopathology of heart gr afts showed predominantly chronic vascular changes with endothelial pr oliferation, intimal thickening and vessel obliteration. No substantia l cellular reactivity in terms of mononuclear/lymphoid cell infiltrati on could be demonstrated in rejected grafts. Spleens and lymph nodes w ere characterized by a profound global reduction in lymphoid tissue af ter preoperative TLI. Although subsequent lymphoid regeneration was de pressed due to postoperative immunosuppression, a significant increase in IgM-positive plasma cells was observed, supporting evidence of an antibody-mediated mechanism of graft rejection. The role of CD4(+) cel ls is unclear, but anti-donor antibody formation might involve T-cell help.