Heterogeneity of Natural Killer Cells

It is now well established that many mammalian species possess leukocytes that are able to lyse a variety of tumors in vitro without prior immunization (1, 2) . These cells have been termed natural killer (NK)t cells . Characterization of the NK cells reactive against different lymphoid and solid tumor targets has revealed that they share certain properties but differ in others . For example, NK activity of spleen cells against the lymphoma YAC-1 is very low in mice injected with the bone-seeking isotope Sr and in mice <3 wk of age (3) . In contrast, NK activity against EL-4 lymphoma cells is relatively unaffected in mice treated with 89Sr and is present in mice 5 d old (4) . However, both the NK (YAC-1) and NK (EL-4) activities are stimulated by interferon inducers administered in vivo (4) . Stutman and coworkers (5, 6) have characterized an NK cell active against solid tumors that they have termed a natural cytotoxic (NC) cell . One notable difference between NC cells and the typical NK cell active against lymphoid tumors is that NC cells remain functional after incubation at 37°C for as long as 6 d, whereas NK cells are labile at 37° C for as few as 6 h under the same culture conditions (5, 6) . These results suggest that NK cells in general may be a heterogenous population . For purposes of discussion, we will designate all non-T, nonB, and non-macrophage cells active in the natural cytotoxicity assay as NK cells and will propose a tentative classification of NK cells . To evaluate the concept of heterogeneity of NK cells, we have used a variety of methods to distinguish between NK cells reactive against a panel of tumors, both lymphoid and nonlymphoid . Our studies, presented here, indicate that NK cells in fresh spleen cell suspensions can be classified into two broad categories on the basis of their susceptibility to suppression by treatment with 89Sr, presence of NK alloantigens, and activity in beige (bg/bg) mice .