Target-effector interactions in the rat NK cell system. II. Effects of interferon on lytic efficiency and on pre-NK cells in various organs, rat strains and during ontogeny.

Interferon (IFN) rapidly stimulates an inactive population of cells (pre-NK) to become lytic and this response to IFN has been used to measure pre-NK cells in the rat. Optimum conditions of IFN dose and time of in vitro exposure were chosen to measure the size of the pool of pre-NK cells in various lymphoid organs, rat strains and during ontogeny using a single cell agarose assay. With increasing dose of IFN there was a small increase in target binding cells, but a marked and similar dose-dependent increase in the number and lytic efficiency of cytotoxic cells. Following enhancement of natural cytotoxicity and antibody-dependent cell-mediated cytotoxicity by IFN, the activity of both functions declined to baseline levels when IFN was removed, but could be restimulated following a second exposure to IFN 24 h later. It was found that the pre-NK cells exhibited the same rat strain and organ distribution as NK cells and had similar physical properties and target cell preferences, suggesting that pre-NK cells and NK cells belong to the same or related cell lineages or are similarly regulated. Cycloheximide has been shown to inhibit the stimulatory effect of IFN on human and murine NK cells whilst not influencing endogenous cytotoxicity. In contrast, we found that both the stimulatory effect of IFN on rat NK cells and endogenous activity were equally inhibited by cycloheximide. Both NK and pre-NK cells could be detected by at least 6 days of age and the pool size of both cell types increased rapidly with age. However, there were comparatively more pre-NK than NK cells in very young rats, although the balance was reversed in adult rats. The implications of these findings are discussed.