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 nonlymphoid tumors has been described in mice and other species, including man. NCMC has been proposed as a 1st level of defense against tumor 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 were 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 were defined: NK cells directed against lymphoma targets and natural cytotoxic (NC) cells directed against solid nonlymphoid tumors. Another distinction between the 2 systems is described. 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 homolog of the Chediak-Higashi syndrome of man. Defective NK activity in blood lymphocytes was also reported in patients with Chediak-Higashi syndrome. Several mouse strains which have low NK activity, have normal or high levels of NC functions, expanding the previous observation that NC and NK cells are under distinct genetic control.