CYTOTOXICITY OF GRAFT-DERIVED LYMPHOCYTES - SPECIFIC FOR DONOR HEART ENDOTHELIAL-CELLS

Background: Previously, we showed that lymphocytes cultured from cardi ac allografts can lyse lymphoid cell lines from donor origin. Because endothelial cells form the first allogeneic barrier to be encountered in vivo, the reactivity of graft-infiltrating cells against donor hear t-derived endothelial cells (DoHEC) may be more relevant for understan ding the clinical course after heart transplantation. Methods: Endomyo cardial biopsies (EMB) were taken at different times after transplanta tion, both during acute rejection and during quiescence. Lymphocytes c ultured from these EMB were assayed for cell-mediated cytotoxicity in a 4-hour chromium 51 release test by use of target panels of different cell types derived from donor or third party. Cell specificity was in vestigated by addition of a tenfold excess of unlabelled target cells to Cr-51-labeled DoHEC. Results: These experiments show that DoHEC can be lysed by lymphocytes derived from EMB. Antigens that were recogniz ed on DoHEC were often donor human leukocyte antigen class I antigens. Some cultures in addition recognized alloantigens present only on DoH EC and not on donor-derived B cells as suggested by lack of or partial inhibition of DoHEC lysis by addition of excess competitor B cells. E ndothelial cell-specific reactivity was unequivocally identified after limiting dilution of EMB-derived cultures. Conclusion: We conclude th at not only DoHEC-reactive but also DoHEC-specific cells are present a mong the cardiac graft infiltrating cells.