Natural cytotoxicity of haemopoietic cell populations against murine lymphoid tumours

Abstract

Summary.-Homozygous nude and normal mice of 3 strains, BALB/c, CBA and C57BL, were used as sources of nucleated haemopoietic "natural killer" (NK) cells. These killer cells could lyse a wide range of syngeneic and allogeneic lymphoid tumour cell lines in vitro, and it was found that cell suspensions from nude mice were always significantly more active than those from normal mice, and that the most active effector population was a polymorph-enriched peritoneal-exudate cell suspension. Eosinophils did not appear to be involved in the phenomenon, and mononuclear peritoneal-exudate cell suspensions were actually highly inhibitory. Three nonlymphoid tumours, a carcinoma, a fibrosarcoma and a mastocytoma, were totally resistant to in vitro lysis. Although all susceptible tumour cell lines were C-type virus-associated, not all of these tumours were killed by all strain sources of spleen cells, indicating a specificity of killing.REPORTS of the in vitro lysis of tumour cells by haemopoietic cells from unimmunized animals and humans have appeared sporadically in the literature. Cell-mediated cytotoxicity, as assayed by the lysis of tumour cell lines, has been reported in a number of different systems using human blood leucocytes (Takasugi, Mickey and Terasaki, 1973; Petranyi et al., 1974), mouse spleen cells Greenberg and Playfair, 1974) and rat spleen cells Holterman, Klein and Casale, 1973) (Kiessling et al., 1975a) an increased incidence in nude mice (Kiessling et al., 1975b) and a lability in tissue culture at 37°C (Herberman et al., 1975b). Recent studies have identified a specific cell-surface alloantigen on the NK cell (Glimcher, Shen and Cantor, 1977) and may provide an approach to its eventual isolation and precise characterization. Studies in a human system have indicated that peripheral human blood leucocytes with natural cytotoxic activity have complement receptors and are not T cells or B cells (Pross and Jondal, 1975); however, the murine natural killer cells lack complement receptors (Kiessling et al., 1976).Studies of the genetic control of this phenomenon have indicated that different mouse strains can manifest either high. or low levels of "natural" cytotoxicity against particular tumour cell lines when their spleen cells are tested in vitro (Zarling et al., 1975). More detailed analysis with congenic mouse lines and backcross analysis has indicated that the phenomenon is under polygenic control, at least one gene of which is linked to the major histocompatibility complex (MHC) (Petranyi, Kiessling and Klein, 1975;Kiessling et al., 1975c), although our own studies described here do not demonstrate any evidence of MHC involvement in the responses studied.This NK-cell phenomenon was first defined with a Rauscher-virus-induced leukaemia and the possible specificity of NK cells for virally determined tumour-associated antigens (TAA) has been widely investigated. It is unlikely that histocompatibility antigens themselves are involved in the antigenic site, as has been suggested for TAAs in other systems (Ge...

An Analysis of the Murine NK Cell as to Structure, Function and Biological Relevance

“…1975a. Virtually all early reports in this field were performed with lymphoid cell lines, and an absolute restriction of lysis sensitivity to tumors of hematopoietic origin has even been suggested (Burton et al 1978). Nunn et al (1977) noted however that several nonlymphoid tumor targets were highly sensitive for NK lysis as well and our group has also found several NK lysis-sensitive tumors of nonlymphoid origin (unpublished results).…”

Heterogeneity of natural killer cells in the mouse.

“…NK Cell Assay. The assays used have been described in detail previously (4,(8)(9)(10)(11) . Approximately 5 X 106 tumor cells were labeled with 100 pCi Nat 51 CrO4 (New England Nuclear, Boston, Mass .)…”

Expression of natural killer (NK) cell‐specific alloantigens on a mouse NK‐like cell line

“…Repeated attempts were made to clone the cells by stepwise decrease of cell density starting from about 4 months in culture, with or without Mitomycin-C treated spleen and thymus cells as feeders. During the 2 years in culture, the NK activity was measured on four separate occasions using our ^'Cr release assay (5) to determine the ability of theC57BL/6 cells to lyse the archetype NK cell target. YAC-1.…”