Mechanisms in organ allograft rejection. An experimental and clinical study

Experimental and clinical aspects of organ allograft rejection were studied. The grafts of ten patients subjected to transplantectomy due to irreversible rejection or viral infection were investigated with immunohistochemistry. T lymphocytes were abundant in the cellular infiltrates of the rejected grafts and cells with 'helper/inducer' phenotype were more numerous than cells with 'suppressor/cytotoxic' phenotype. The expression of HLA-DR antigens was found to differ from that of HLA-DQ antigens in healthy human kidneys as well as in infected or rejected kidney grafts. HLA-DR but not -DQ antigens were thus detected in proximal tubular cells and increased during rejection or infection. Serum levels of interferon were found to be related to the occurrence of clinical signs of rejection or viral infection in renal transplant patients. Class II MHC antigen expression and cellular infiltrates were immunohistochemically characterized in untreated rejecting rat kidney grafts and were compared to the reactions of syngeneic renal grafts in the same model. The infiltrates of the syngeneic grafts were smaller and occurred later than those of the allografts and were dominated by cells with the 'helper/inducer' T cell phenotype. The number of class II antigen expressing renal tubules was markedly increased in allogeneic grafts and, to a lesser extent, also in syngeneic grafts. The effects of different monoclonal T cell antibodies were investigated in a rat heart allograft model. A 'pan' T cell antibody and a 'suppressor/cytotoxic' T cell antibody significantly prolonged graft survival and caused expression of class II antigen as well as of T cell 'suppressor/cytotoxic' antigen on graft parenchymal cells. Permanent survival of heart grafts could be achieved after induction with antithymocyte globulin. Grafts functioning for more than eight months were found to have myocardial fibrosis, intimal thickening and fibrosis of vessels, mild lymphocyte infiltration and increased class II antigen expression. The changes observed were similar to those seen in chronic rejection.