DETECTION OF DONOR-SPECIFIC HYPORESPONSIVENESS FOLLOWING LATE FAILUREOF HUMAN RENAL-ALLOGRAFTS

Limiting dilution assays to measure the frequency of interleukin-2-sec reting peripheral blued T cells were carried out in patients, whose re nal allografts had failed due to acute rejection (9 patients) and in p atients whose grafts failed more than two years after transplantation without any recent evidence of acute rejection. Using a modified form of the assay we demonstrate that nearly half of 18 patients whose rena l transplants had failed after more than two years have low or undetec table HTLp frequencies against donor, but not third-party DR antigens. No such difference was observed in any of the nine patients studied w hose transplants were lost from early acute rejection. These results p rovide the first indication that, as in rodent models of transplantati on, T cell unresponsiveness towards donor MHC antigens can occur follo wing prolonged residence of an allograft in humans, Furthermore, the r esults suggest that chronic rejection may be driven by mechanisms othe r than direct allorecognition. The assay may be a valuable tool to stu dy the evolution of donor-specific direct T cell alloresponsiveness in patients with well-functioning grafts.