Donor-specific cytotoxicity testing: an advance in detecting pulmonary allograft rejection

Ten beagle dogs underwent left unilateral lung transplantation and were treated with cyclosporine and azathioprine. After three days, cyclosporine administration was discontinued and azathioprine administration was maintained at a suboptimal dose to allow a graded response to the pulmonary allograft. Dogs were monitored by chest roentgenogram, bronchoalveolar lavage (BAL), and sampling of peripheral blood lymphocytes at weekly intervals. Open lung biopsies also were performed at weekly intervals in 5 of the dogs. Lymphocytes from the BAL and peripheral blood and those grown in culture from open and transbronchial biopsy specimens were tested for donor-specific cytotoxicity (DSC) by testing their responsiveness to lymphocytes from their donor. Rejection was confirmed in all animals. Donor-specific cytotoxicity became detectable in all animals in either the BAL fluid or biopsy specimens. An abnormal chest roentgenogram developed in 9 dogs, but not until after DSC was detected in the BAL in 7. In the open biopsy specimens tested for DSC, all exhibited DSC synchronous with the first changes noted on chest roentgenogram. Donor-specific cytotoxicity was sensitive for detecting rejection in 8 of 9 dogs in the BAL and in 5 of 5 dogs in the open biopsy specimens. Based on these results, 3 additional dogs were maintained on cyclosporine. Two of these dogs did not reject their transplants and had no evidence of DSC. We conclude that donor-specific functional assays provide an advance over less sensitive clinical techniques.