752 on the Heterogeneity of Natural Killer Cells

In the mouse, a number of serological markers are reported to be expressed on natural killer (NK) x cells, including NKI (1, 2), Ly-5 (3), Qa-2, Qa-4, and Qa-5 (4, 5), asialo GM1 (6), Thy1 (7), and Mph1 (8). The conflicting evidence on the phenotypes and characteristics of NK cells in various systems can best be reconciled if NK cells are not a single cell type derived from a common lineage, but represent a heterogeneous population of cells sharing the capability of selective cytotoxicity. The possibility that NK cells were heterogeneous was initially suggested by the important experiments of Stutman et al. (9, 10) and Burton (2), which indicated that spontaneous cytotoxic effector cells active on solid tumor cells have characteristics different from the NK cells that kill lymphoma cell targets, e.g., cell surface markers, organ distribution, strain distribution, and radiation sensitivity. Kumar et al. (I 1) observed that mouse NK activity on EL4 target cells had different sensitivity to bone marrow irradiation by 89Sr from that on YAC tumor cells. Lohman-Matthes et al. (8) reported that cultured bone marrow cells could exert NK-like activity, and that such cells shared common surface antigenic determinants with mononuclear phagocytes. In previous work (12), we have attempted to define some of the genetically determined serological markers on mouse NK cells effective against virus persistently infected xenogeneic tumor cells and, using such markers, were able to show that interferon acts on a precursor cell stimulating its differentiation into a cytolytic effector NK cell. In the present report we have analyzed the heterogeneity of N K cells in mice and identified at least four phenotypieally distinct cytotoxic effector cells that differ not only in their surface markers, but also in their responsiveness to the regulatory influences of interferon (IFN) and interleukin 2 (IL-2).