Donor‐specific Immune Regulation by CD8+ Lymphocytes Expanded from Rejecting Human Cardiac Allografts

To assess whether regulatory T cells are present in rejecting human cardiac allografts, we performed functional analyses of graft lymphocytes (GLs) expanded from endomyocardial biopsies (EMB; n = 5) with histological signs of acute cellular rejection. The GL cultures were tested for their proliferative capacity and regulatory activity on allogeneic‐stimulated peripheral blood mononuclear cells (PBMC) of the patient (ratio PBMC:GLs = 5:1). Three of these GL cultures were hyporesponsive to donor antigens and suppressed the antidonor proliferative T‐cell response of PBMC, but not the anti‐third‐party response. Interestingly, it was the CD8+ GL subset of these cultures that inhibited the antidonor response (65–91% inhibition of the proportion of proliferating cells); the CD4+ GLs of the expanded GL cultures were not suppressive. In conclusion, CD8+ GLs expanded from rejecting human cardiac allografts can exhibit donor‐specific immune regulatory activities in vitro. We suggest that during acute cellular rejection, GLs may not only consist of graft‐destructing effector T cells, but also of cells of the CD8+ type with the potential to specifically inhibit antidonor immune reactivity.