Heterogeneity of natural killer cells in the mouse.

Abstract

Mice were treated with the bone-seeking isotope, 89Sr, cyclophosphamide, and short-term lethal irradiation in vivo, and murine spleen cells are treated with anti-Nk-1.2 plus complement (C) in vitro. Fresh spleen cell suspensions from the above groups and from beige and neonatal mice were subsequently tested for natural killer (NK) cell activity against a panel of lymphoid and nonlymphoid tumor cell target. NK cell reactivities against YAC-1, MPC-11, and Cl.18 tumors were markedly and consistently reduced in (a) mice treated with 89Sr, (b) spleen cells treated with anti-Nk-1.2 plus C, and (c) C57BL/6 bg/bg mice. In contrast, NK activities against FLD-3 and WEHI-164.1 tumors were usually normal in mice treated with 89Sr, in beige mutant mice, and in spleen cells after treatment with anti-Nk-1.2 antibody and C. It appears, therefore, that two major groups of NK cells exist in fresh mouse spleen cells suspensions. NK-A cells are marrow dependent, Nk antigen positive, and deficient in beige mice; these lyse YAC-1, MPC-11, and Cl.18 tumors. NK-B cells, which are responsible for the lysis of WEHI-164.1 and FLD-3, are Nk antigen negative, marrow independent, and unaffected by the bg/bg mutation. Other features of NK-B cells, suggest that these NK cells, although they share the characteristics mentioned above, differ among themselves especially with respect to age of maturation and susceptibility to cyclophosphamide and total body irradiation. The NK-B group may therefore induce subsets that remain to be defined.

Natural cytotoxic cells against solid tumors in mice. IV. Natural cytotoxic (NC) cells are not activated natural killer (NK) cells

“…These results generally support the conclusions from our previous work (Stutman et al, , 1980a(Stutman et al, , b, 1981Paige et al, 1978;Stutman and Cuttito, 1980;Lattime et al, 1981;Stutman and Cuttito, 1981) as well as work from other laboratories (Kumar et al., 1979;Burton, 1980;Lust et al, 1981;Minato et al, 1981) which indicate that at least two distinct effector cell populations, NC and NK, are involved in murine NCMC against a variety of tumor cell lines.…”

“…The results obtained from these studies are consistent with our interpretation that NC and NK cells are distinct populations which together make up a heterogeneous NCMC system (Stutman et al, , 1980bPaige et al, 1978;Stutman and Cuttito, 1980;Lattime et al, 1981;Kumar et al, 1979;Burton, 1980;Minato et al, 1981;Lust et al, 1981).…”

Murine non‐lymphoid tumors are lysed by a combination of NK and NC cells

“…While we have identified all three types of non-lymphoid targets, we have yet to find a lymphoid target which is lysed by NC-cell activity, although a lymphoma which is lysed by effector cells resembling the NC cell has been described (Lust et al, 1981). Target cell lines were considered to be "NK-sensitive" if more than 90% of all activity was due to a Qa-5+ effector cell and "NC-sensitive" if more than 90% of all activity was due to Qa-5-effector cell.…”

Lysis of fld‐3 friend erythroleukemia cellsin vitroandin vivo: Effect of89sr treatment and friend virus infection

“…FLD-3 (H-2d) erythroleukemia cells were obtained from Dr. Richard A. Steeves (Albert Einstein School of Medicine, New York). All of the above tumor cell lines were maintained in vitro by culturing in RPMI-1640 with 10% fetal calf serum, penicillin, streptomycin and L-glutamine (complete RPMI) as previously described (Lust et al, 1981).…”

“…To assess the relevance of NK cells in mediating tumor resistance in vivo, many studies have utilized cytotoxic activity against YAC-1 thymic lymphoma as a non-specific in vitro correlate of in vivo NK activity. However, NK(YAC-1) activity may not always be relevant to resistance against a given unrelated tumor, especially since NK cells reactive against different tumors appear to be heterogeneous with respect to cell surface markers, differentiation and possibily regulatory mechanisms (Lust et al, 1981;Minato et al, 1981;Paige et al, 1978). Those cytolytic effectors expressing NK-2 alloantigens, which are defective in bglbg (beige) mice and deficient in mice depleted of functional marrow tissue (89Sr or estradiol treatment) will be considered here as NK cells, while effectors lacking those properties will be termed natural cytotoxic (NC) cells for purposes of discussion.…”