In vitro reactivity of natural killer (NK) cells against Cryptococcus neoformans.

Abstract

Natural cell-mediated cytotoxicity (NCMC) has been identified as one of the body's first lines of defense against neoplastic cells, and NCMC possibly functions in some viral infections and in regulating the development and differentiation of normal tissues. A subpopulation of lymphocytes known as natural killer (NK) cells has been shown to be one of the effector cells in this natural surveillance system. Up to this time the effects of NK reactivity on cells of nontissue origin have not been reported; therefore, the primary objective of this study was to examine the effects of cells with characteristics on NK cells on the growth in vitro of a yeast-like organism Cryptococcus neoformans. Using unstimulated murine nylon wool-nonadherent splenic cells as effector cells, we simultaneously determined the in vitro NK reactivity using a 4-hr 51Cr-release assay with YAC-1 targets and the ability of the effector cells to inhibit the growth of C. neoformans in vitro. In a series of experiments, the levels of NK reactivity were varied by using high and low NK-reactive strains of mice, different ages of mice, and NK-augmenting and depressing agents. We found that the level of NK reactivity of the effector cell pools correlated with the ability of effector cells to limit the growth of the cryptococci. For example, high NK-reactive cell pools from young CBA/N mice were more effective in inhibiting the growth of seven different isolates of C. neoformans than were low NK-reactive splenic cells from young A.TH mice. In addition, splenic cells from 7-wk-old CBA/N mice with high levels of NK activity inhibited cryptococci growth more effectively than splenic cells from 20-wk-old CBA/N animals with low NK activity. Poly I:C, an NK stimulating substance, boosted NK and growth inhibitory activities simultaneously in the spleens of treated mice. In addition, when old CBA/N mice were treated i.v. with 0.7 mg of C. parvum, an agent that augments NK cell activity at 3 days after treatment then depresses NK activity by 7 days, we found that the growth inhibitory ability of the spleen cells paralleled the rise and fall of NK cell reactivity. The lymphoid cells responsible for the Nk activity in the 4-hr 51Cr-release assay and for the activity in the cryptococci growth inhibition assay were characterized as being nylon wool-nonadherent, Thy-1-, surface Ig-, Ia-, and asialo GM 1-positive, supporting the contention that NK cells were responsible for the in vitro inhibition of growth of C. neoformans. These data suggest that NK cells may play a role in natural host defense in cryptococcosis.