[Detection of donor specific cytotoxic T lymphocyte activity in lung grafted mongrel dogs].

Cytotoxic activity against donor skin fibroblasts in peripheral blood mononuclear cells was evaluated by using 10 mongrel dogs with left lung allografts and the results obtained herein were as follows. 1) Culture of skin fibroblasts primarily separated with collagenase and disperse was feasible to grow monolayers within several days to 1 weeks. Four hour responding time of mononuclear cells to targets was superior to 18 hour responding time, with the reproducibility of this assay under the 4 hour cocultivation between effectors and targets. 2) The effectors in this assay established in our laboratory were the cells nonadherent on plastics and nylon wool, suggesting T lymphocytes and donor specificity was confirmed by cold competition. 3) This donor specific cytotoxic activity derived from T lymphocytes was steeply elevated 4 to 8 days postoperatively with the average of 6 days in rejecting lung allografts and histologic examination revealed edema and fibrin-like substance in alveolar space. Cyclosporin A, however, could remarkably suppress its activity and grafted lung maintained function. In conclusion, the effectors in cytotoxic activity against donor skin fibroblasts in lung allografted mongrel dogs developed in our laboratory revealed as donor specific cytotoxic T lymphocytes and this assay is very useful to demonstrate rejection, the effect of immunosuppressive drugs and the differentiation between rejection and infection.