In vitro studies of the cell-bound and antibody-mediated immunity evoked by murine renal allotransplants. Influence of presensitization, total body irradiation and immunosuppressive agents.

The influence of presensitization, total body irradiation and several immunosuppressive drugs on the immune response evoked by allogeneic rat kidneys was studied and . The cytotoxic effect of recipient thoracic duct lymphoid cells and fresh or heat-inactivated recipient serum against donor target cells was measured with Cr assay. Rats that had undergone two consecutive allogeneic transplantations from isogenous donors had thoracic duct lymphoid cells and serum with an increased cytotoxic effect against donor strain target cells as compared to control rats transplanted only once. Heat-inactivated recipient serum from such animals also had an increased blocking effect on cell-mediated cytotoxicity. ALS had the strongest depressive effect on the cell-bound immunological responses evoked by the transplants in the recipient rats, decreasing both the number of lymphoid cells in the thoracic duct lymph and the cytotoxic activity of the remaining cells. Methylprednisolone and methotrexate also strongly suppressed the cellular immunological events in the way just mentioned. Actinomycin-C and total body irradiation depressed cell-bound immune response only by causing a decrease in the number of cells in the thoracic duct lymph. Azathioprine did not influence cell-bound immunological responses to allogeneic kidney transplants. Total body irradiation, methotrexate and methylprednisolone treatment markedly diminished the cytotoxic effect of fresh recipient serum against target cells and reduced the blocking effect of heat-inactivated recipient serum on lymphoid cell-mediated cytotoxicity. The other tested agents all caused a moderate depression of the cytotoxic and blocking effect of fresh and heat-inactivated recipient serum, respectively. When folinic acid was given regularly between consecutive methotrexate injections, the depression of the lymphoid cell amount in the thoracic duct lymph was markedly less. The results of the cytotoxicity tests were similar to those obtained with methotrexate treatment alone.