T-cell receptor-negative natural killer cells display antigen-specific cytotoxicity for microvascular endothelial cells

Based upon prior demonstrations that human microvascular endothelial cells (ECs) could serve as natural killer (NK) cell targets, we established NK cell lines and clones by repeated stimulation of highly purified CD16-positive, CD3/T-cell receptor (Ti)-negative cells with allogeneic ECs. After 3 weeks in culture these lymphoid cells, which neither expressed surface CD3/Ti molecules nor rearranged Ti β- or γ-chain genes and which lysed K562 human erythroleukemia cells, displayed specific cytotoxicity for the stimulating ECs. Furthermore, freshly isolated NK cells bound and then removed from each of several allogeneic EC lines displayed selective cytotoxicity for the adsorbing EC line. These results provide evidence for alloantigen-specific recognition of microvascular ECs by NK cells that appears to be determined, at least in part, at the level of adherence. We discuss the implications of these findings with respect to the rejection of vascularized organ allografts.