Natural killer cells: Endothelial interactions, migration, and target cell recognition

Abstract: Natural killer (NK) cells form a unique third group of lymphocytes that differs from T and B cells in surface phenotype, target recognition, and function. By producing cytokines and exerting cyto-toxicity, NK cells participate in the resistance against microbial infections and malignant disease. The re-search on the molecular mechanisms of migration and target cell recognition by NK cells has recently devel-oped rapidly. NK cells express a number of adhesion molecules common to hematopoietic lineage, bind to endothelium, extravasate, and respond to chemotactic stimuli, much resembling T cells in those respects. However, NK cells are probably capable of transmigra-tion and infiltration merely through activation by cytokines and chemokines, as opposed to the require-ment of antigen presentation in the initial activation of I cells. Target cell recognition and ensuing cytotoxic-ity of NK cells is a sum effect of a delicate balance between the effects of inhibitory and activating NK cell receptors. NK cells express several well-defined MHC I-recognizing receptors that inactivate their functions. In pathological alterations of MHC I expres-sion, the inhibitory receptors do not engage and thus permit the lysis of the target cell. The receptors that trigger the cytolytic machinery of NK cells are less well known. Some candidate triggering receptors have been identified and it seems that NK cell triggering is mediated by multiple receptors, as is the inhibition of cytotoxicity. For example, NK cells clearly detect tar-get cell-bound antibodies and thus mediate antibody-dependent cytotoxicity. They may also detect carbohy-drate moieties, normal but pathologically distributed adhesion molecules, as well as ligands for a number o