Natural cell‐mediated cytotoxicity in rats. II. In vivo augmentation of NK‐cell activity

Abstract

Natural cell-mediated cytotoxicity in rats as well as in mice has been shown to vary consistently with age, with peak levels detectable at 5-10 weeks. The levels of cell-mediated cytotoxicity against tumor cells could be augmented in strains of inbred rats with either high or low levels of natural reactivity, by IP injection of a variety of agents, including C. parvum, LCMV, KRV, and poly I:C. The specificity of the augmented cytotoxicity appeared to be the same as the specificity of natural killer cells which are found in normal rat spleen cells. Similarly, the cells mediating the augmented cellular cytotoxicity were small, non-adherent, esterase-negative lymphocytes with Fc receptors, as are rat NK cells. The kinetics and organ distribution of the augmentation of NK activity by poly I:C and C. parvum were compared and the kinetics were found to differ, with a shorter time course of augmented activity seen after inoculation with poly I:C. These data indicate that interferon may play a central role in the augmentation of NK activity in vivo.

Spontaneous development of cytotoxic activity in cultured lymphnode cells from tumour-bearing rats

“…(1976) have described a different cytotoxic activity which developed in normal mouse spleen cells over a 5-day culture period and was of broad specificity. Ortaldo et al (1977) made similar observations with human peripheral blood cells, and showed that in this system the cytotoxicity was generated by substances in foetal calf serum, suggesting some kind of mitogenic or antigenic activation. Indeed, these workers, and subsequently others (Callewaert et al, 1978) demonstrated that stimulation of human peripheral blood lymphocytes with phytohaemagglutinin, PPD, or allogeneic cells induced high levels of spontaneous cytotoxicity, which was mediated by an Fc+ cell (Ortaldo et al, 1977).…”

“…Ortaldo et al (1977) made similar observations with human peripheral blood cells, and showed that in this system the cytotoxicity was generated by substances in foetal calf serum, suggesting some kind of mitogenic or antigenic activation. Indeed, these workers, and subsequently others (Callewaert et al, 1978) demonstrated that stimulation of human peripheral blood lymphocytes with phytohaemagglutinin, PPD, or allogeneic cells induced high levels of spontaneous cytotoxicity, which was mediated by an Fc+ cell (Ortaldo et al, 1977). A third type of cytotoxicity developing in culture has been described by Muchmore et al (1977a), human peripheral blood cells developing spontaneous cytotoxicity towards red blood cells when cultured alone for 7 days.…”

“…Tumour growth therefore played an important part in the induction of the cytotoxic cells. It is interesting to note that the activity of conventional NK cells (Herberman & Holden, 1978) can be augmented by certain in vivo treatments, including the inoculation of tumour cells Oehler et al, 1978). However, tumour growth itself has been reported to depress NK-cell activity (Becker & Klein, 1976;Pross & Bains, 1976).…”

Factors affecting stimulation of natural cytotoxicity to a rat lymphoma by Corynebacterium parvum

“…However, different effects oin cytotoxicity have been observed; whilst i.p. inoculation of C. parvum augmented splenic cytotoxicity in mice (Herberman et al, 1977) and rats (Oehler et al, 1978) others have reported minimal effects on cytotoxicity in the spleen using this rouite of inoculation, in contrast to the marked depression of splenic cytotoxicity after i.v. inoculation (Ojo et al,1 978a).…”

“…stimulates cytotoxicity in mice (Herberman et al, 1977;Ojo et al, 1978a;1,978b) and rats (Oehler et al, 1978) attributable to non-adherent non-T cells which closely resemble the NK cells of normal animals. However, different effects oin cytotoxicity have been observed; whilst i.p.…”