THE DETECTION OF CYTOTOXIC T-CELLS WITH HIGH-AFFINITY RECEPTORS FOR DONOR ANTIGENS IN THE TRANSPLANTED HEART AS A PROGNOSTIC FACTOR FOR GRAFT-REJECTION

Alloreactive T lymphocytes are the initiators and effecters of acute r ejection of organ transplants, and T cells with high-affinity receptor s for antigen might be especially implicated in this process. It has b een shown that the cytotoxic capacity of CTL with low affinity for all oantigens can be inhibited with CD8 mAb, while high-affinity CTL are n ot affected. To investigate whether the presence of such high-affinity cells in human heart transplants may be predictive for acute rejectio n, we analyzed their frequency in cultures derived from endomyocardial biopsies in 19 patients, 9 of whom had never experienced acute reject ion and 10 who had had one or more rejection episodes. In the rejector s, already before histological signs of rejection (myocyte damage) had developed, significantly higher donor-reactive CTL frequencies were f ound compared with the nonrejectors (medians of 10,586 vs 1,169 reacti ve cells per 10(6) tested cells, P=0.002). After CD8 inhibition, the d ifference between rejectors and nonrejectors was even more pronounced (P<0.001). In patients with rejection, the number of CDS-resistant, hi gh-affinity CTL was higher than 1000 per million cells in all cases, w hile in patients who had never experienced rejection this number was l ess than 1000. As these CTL characteristics are already present before the first histological signs of rejection have developed, this might be used as a prognostic factor.