Cytotoxicity of graft-derived lymphocytes: specific for donor heart endothelial cells?

Previously, we showed that lymphocytes cultured from cardiac allografts can lyse lymphoid cell lines from donor origin. Because endothelial cell form the first allogeneic barrier to be encountered in vivo, the reactivity of graft-infiltrating cells against donor heart-derived endothelial cells (DoHEC) may be more relevant for understanding the clinical course after heart transplantation.

Endomyocardial biopsies (EMB) were taken at different times after transplantation, both during acute rejection and during quiescence. Lymphocytes cultured 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 investigated by addition of a tenfold excess of unlabelled target cells to 51Cr-labeled DoHEC.

These experiments show that DoHEC can be lysed by lymphocytes derived from EMB. Antigens that were recognized on DoHEC were often donor human leukocyte antigen class I antigens. Some cultures in addition recognized alloantigens present only on DoHEC 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. Endothelial cell-specific reactivity was unequivocally identified after limiting dilution of EMB-derived cultures.

We conclude that not only DoHEC-reactive but also DoHEC-specific cells are present among the cardiac graft infiltrating cells.