Natural killer cells mediate lysis of embryonal carcinoma cells lacking MHC

Abstract

Mouse teratocarcinomas are tumours of the germ cells¹ whose tumorigenicity is a property of a pluripotent stem cell type denoted the embryonal carcinoma (EC) cell. These cells seem to be analogous to cells of the early mouse embryo and will indeed contribute to the normal development of a mouse if injected into blastocysts². EC cells display an unusual transplantation behaviour and can frequently be grafted, giving tumours in several different mouse strains³. Thus, the protective immune mechanisms against such tumours may be less efficient than, and/or of a different nature from, those against most other tissues. Cytolytic T cells generally fail to kill EC cells^4–6, although there is one report of the apparent induction of specific anti-EC T-killer cells⁷. The failures^4–6 are easily explained as being due to the absence of major histocompatibility complex (MHC) products on the surface of ECs^3,8. Recently, however, a new cell type, the natural killer (NK) cell, has been shown to have potent lytic activity when tested against several tumour targets^9–11. Targets of NK cells also include normal thymocytes¹² and certain stem cells of the bone marrow¹³. As NK cells seem to display a select but distinct specificity pattern from T lymphocytes and because NK targets include normal cells at an ‘immature’ stage of differentiation, we considered it possible that NK cells provide an alternative to T cells in producing cell-mediated immune reactions against teratocarcinomas. Here we report that murine NK cells are highly efficient cytolytic aggressors to EC cells whereas more differentiated cell lines derived from the latter are less susceptible or completely resistant.