Natural cell-mediated cytotoxicity (NCMC) capable of in vitro lysis of various lymphoid and non-lymphoid tumours has been described in mice and other species, including man. NCMC has been proposed as a first level of defence against tumour growth in vivo, one which does not need the priming of the conventional immunological response. The effector cells of NCMC seem to belong to a special category of lymphoid cells, being neither classical T or B cells nor macrophages; natural killer (NK) cells have been proposed as the prototype effector cell, although some heterogeneity among effector cells seems to exist, depending on the target cells used for testing. Two main subgroups of NCMC effector cells have been defined: NK cells directed against lymphoma targets and natural cytotoxic (NC) cells directed against solid non-lymphoid tumours. We describe here another distinction between the two systems: while NK activity is low in mice homozygous for the beige (bg) gene NC activity in spleen cell preparations from these animals is comparable with that observed in the appropriate controls (bg/+ and +/+ littermates). The bg syndrome of mice affects lysosome, melanosome and enzymatic functions and is a homologue of the Chediak--Higashi syndrome of man. Defective NK activity in blood lymphocytes has also been reported in patients with Chediak--Higashi syndrome. We also show that several mouse strains which have low NK activity, have normal or high levels of NC functions, expanding our previous observation that NC and NK cells are under distinct genetic control.

Natural cell-mediated cytotoxicity (NCMC) against a variety of tumor targets is mediated by a heterogeneous group of effector cells with the natural killer (NK) and natural cytotoxic (NC) cells being the predominant prototypes in mice. This report shows that non-lymphoid tumor targets, mostly derived from chemically induced fibrosarcomas, are susceptible to either (1) NK-mediated lysis with all the activity being the function of a poly-IC augmentable Qa-5+ effector cell; (2) NC-mediated lysis with all activity being the function of a Qa-5- cell not augmented by poly-IC; and (3) a combination of NK-and NC-mediated lysis with activity being the function of both Qa-5+ and Qa-5- cells, the NK (Qa-5+) augmented by poly-IC. These studies further support the view that murine NC and NK cells are distinct and collectively make up the NCMC system, and also that the previous association of NK cells with lymphoid tumor lysis and NC cells with non-lymphoid tumor lysis is not a valid one.

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