Normal levels of natural cytotoxic cells against solid tumours in NK-deficient beige mice

Abstract

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.