Human cytotoxic effector cells: definition and analysis of activity

Abstract

Studies have indicated that the complexity of NK and LAK activities goes beyond the question of which effector cell mediates most of this activity. Examination of Nk activity reveals that numerous effector phenotypes can mediate spontaneous, non-MHC-restricted cytotoxicity. These effector cells are predominantly the CD3-, Leu19 (NKH1)+ and the CD3+, Leu19 (NKH1)+ lymphocytes. However, the existence of other effector cells capable of mediating NK activity and the relative contribution of each type of effector cell in vivo situations requires further study. In addition, LAK activity has been attributed to numerous cell types, and an indepth examination of the regulation and recognition events involved in LAK activity indicates a greater degree of heterogeneity than was initially anticipated. The preliminary data presented above support the contention that although NK and LAK activities are quite similar with regard to their lytic properties (e.g. effector phenotype, target selection), their mechanisms of targets cell recognition and lytic attack appear to be quite different. Our investigation of recognition events indicated that IL-2-activated effector cells do not recognize the same structure that is recognized by freshly isolated NK cells. These data suggest that a recognition event occurs on activated cells that can be dissociated from the events involved in NK binding by fresh CD3- LGL. With regard to CD3+ effectors, the role of the TcR and the nature of the receptor mediating LAK activity require further study to determine whether multiple receptors or a single, unique receptor class are expressed after IL-2 stimulation. In addition, the role of IFN gamma and other regulatory cytokines must be further examined to determine their importance in human LAK activity.