Natural cell-mediated cytotoxicity in rats. III. Effects of immunopharmacologic treatments on natural reactivity and on reactivity augmented by polyinosinic-polycytidylic acid

Abstract

Treatment of rats with high doses of hydrocortisone, X-irradiation, or cyclophosphamide had a suppressive effect on natural cytotoxicity in vivo. However, when rats were given poly I:C after any of these agents, the levels of NK activity were similar to those in normal rats which had been given poly I:C alone. To explain these findings, we have postulated that a population of pre-NK cells, resistant to hydrocortisone, cyclophosphamide and X-irradiation was induced by poly I:C to become cytotoxic NK cells. Treatment of rats with silica, in doses that had no effect on proliferative responses of host lymphocytes to Con A in vitro, sharply diminished NK activity. With this agent, the boosting effect of poly I:C, although still detectable, was diminished. Since there is little if any indication that NK cells are phagocytic, these data suggest that phagocytes may play a role in maintaining high levels of NK activity in vivo and, further, may be involved in the mechanism by which natural cytotoxicity is boosted by poly I:C. Adult thymectomized rats had easily detectable levels of natural reactivity and the response to poly I:C was unimpaired, indicating a lack of thymic dependence for boosting as well as for spontaneous levels of NK activity.