Anti‐CD4 monoclonal antibody treatment in combination with total lymphoid irradiation and cyclosporin A in hamster‐to‐rat cardiac transplantation

Significantly prolonged graft survival (GS) of hamster hearts transplanted heterotopically into rats can be achieved by different immunosuppressive treatment strategies. The exact mechanism of graft rejection is unclear, but it seems to be a primarily humoral, antibody-mediated type of rejection. The histopathology of long-term surviving grafts is controversial and the morphology of lymphoid tissue in spleens and lymph nodes as the possible site of anti-donor antibody formation has not previously been investigated. This report demonstrates a significantly prolonged GS in hamster-to-rat cardiac transplantation after combined treatment with total lymphoid irradiation (TLI), cyclosporin A (CyA) and anti-CD4 monoclonal antibodies (MAb), where long-term GS (> 100 days) could be achieved in a few animals. The histopathology of heart grafts showed predominantly chronic vascular changes with endothelial proliferation, intimal thickening and vessel obliteration. No substantial cellular reactivity in terms of mononuclear/lymphoid cell infiltration could be demonstrated in rejected grafts. Spleens and lymph nodes were characterized by a profound global reduction in lymphoid tissue after preoperative TLI. Although subsequent lymphoid regeneration was depressed 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+ cells is unclear, but anti-donor antibody formation might involve T-cell help.