Low natural in vivo resistance to syngeneic leukaemias in natural killer-deficient mice

Abstract

Natural killer (NK) cells, which occur at high levels in normal non-immune individuals of several species, have the capacity to lyse certain tumour cells in vitro, and have been proposed as a first level of defence against tumour growth in vivo^1–3. Evidence for this comes mainly from the murine system, where certain FI hybrid or T-cell deficient mice with high NK activity resist growth of transplanted tumours better than do normal syngeneic controls with lower NK activity^4–6. Recent studies of the beige mutation on the C57BL mouse strain background, previously proposed as an animal homologue of the human Chediak-Higashi syndrome^7,8, have revealed a new model for analysing anti-tumour effector mechanisms in the intact syngeneic host^9,10. The recessive beige gene (bg^J), which affects melanosome and granulocyte lysosome functions^11,12, also causes a profound (but not total) depression of NK activity whereas other anti-tumour effector mechanism mediated by T cells and macrophages remain relatively intact¹³. It was important, therefore, to test the tumour susceptibility of beige mice as a first direct test of the hypothesis that NK cells are involved in surveillance against neoplasia. In partial confirmation of this hypothesis, we report here that failure of small threshold doses of one virally and one chemically induced transplantable leukaemia to grow out in syngeneic mice partly depends on a rapidly acting host defence mechanism. This mechanism is deficient in bg/bg mice, which develop palpable, progressively growing tumours faster and at a higher frequency than do phenotypically normal +/bg littermates.