Comparison of natural killer and natural cytotoxic cells: characteristics, regulation, and mechanism of action.

NK cells are distinct cell populations that can be defined by a series of functional and surface characteristics. The existence of the discrete morphological counterpart for the NK cell, the LGL, has made it particularly convenient for categorizing these effector cells and distinguishing them from a variety of other effector cells. In addition, similar to T cells, considerable diversity exists among the NK cells. The diversity is seen not only in the expression of different surface markers but also within the specificity of target recognition as well as the secretory ability of LGL. It remains possible that much or even all of the heterogeneity that is seen in the phenotype and the function of LGL is due to differences and phases of activation and/or differentiation of these cells. Such differentiation-dependent, non-clonal, heterogeneity appears to account for the heterogeneity seen in subsets of monocytes and macrophages which can be detected in the expression of Ia antigen and Fc gamma receptors on activated macrophages. NK activity is highly regulated by IFNs (alpha, beta) and IL-2. Since NK cells also produce these factors, an autocrine regulation of these cells or their activity may occur. In addition, the mechanism of NK lysis is not yet clearly defined, but seems to involve cytotoxic molecules present in cytoplasmic granules that are released in various forms after effector-target cell contact. In contrast, NC activity against the WEHI-164 target cells appears to be a cytokine-mediated phenomenon, apparently mediated by the release of TNF during the course of the cytotoxicity assay. The mediation of NC activity by the release of TNF may account for the usual requirement for prolonged incubation periods to demonstrate this activity, in contrast to the rapid kinetics of NK activity. The association of TNF with NC activity also provides new clues about the nature of the NC cell, since TNF has been found to be produced predominantly by macrophages but can also be released by lymphocytes.