The Detection Of Cytotoxic T Cells With Highaffinity Receptors For Donor Antigens In The Transplanted Heart As A Prognostic Factor For Graft Rejection

Abstract

Alloreactive T lymphocytes are the initiators and effectors of acute rejection of organ transplants, and T cells with high-affinity receptors for antigen might be especially implicated in this process. It has been shown that the cytotoxic capacity of CTL with low affinity for alloantigens can be inhibited with CD8 mAb, while high-affinity CTL are not affected. To investigate whether the presence of such high-affinity cells in human heart transplants may be predictive for acute rejection, we analyzed their frequency in cultures derived from endomyocardial biopsies in 19 patients, 9 of whom had never experienced acute rejection and 10 who had had one or more rejection episodes. IN the rejectors, already before histological signs of rejection (myocyte damage) had developed, significantly higher donor-reactive CTL frequencies were found compared with the nonrejectors (medians of 10,586 vs 1,169 reactive cells per 10(6) tested cells, P = 0.002). After CD8 inhibition, the difference between rejectors and nonrejectors was even more pronounced (P < 0.001). In patients with rejection, the number of CD8-resistant, high-affinity CTL was higher than 1000 per million cells in all cases, while in patients who had never experienced rejection this number was less 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 factors.