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.

CpG motifs present in bacteria DNA rapidly induce lymphocytes to secrete interleukin 6, interleukin 12, and interferon gamma.

“…A 6-base DNA motif consisting of an unmethylated CpG dinucleotide flanked by two 5' purines and two 3' pyrimidines was shown to contribute to this response by inducing polyclonal B-cell (3,4,(7)(8)(9)11). Recent work from our laboratory suggested that this B-cell stimulation was mediated by a 6-base nt motif consisting of an unmethylated CpG dinucleotide flanked by two 5' purines and two 3' pyrimidines (12).…”

“…Yamamoto and others (5)(6)(7)(8)(9) showed that bacterial but not mammalian DNA boosted the lytic activity of natural killer (NK) cells and induced interferon y (IFN-y) production, effects attributed to palindromic sequences present in bacterial DNA (5,10). Other investigators showed that bacterial DNA, especially when complexed to DNA-binding proteins, induced B-cell activation (3,4,(7)(8)(9)11).…”

“…Other investigators showed that bacterial DNA, especially when complexed to DNA-binding proteins, induced B-cell activation (3,4,(7)(8)(9)11). Recent work from our laboratory suggested that this B-cell stimulation was mediated by a 6-base nt motif consisting of an unmethylated CpG dinucleotide flanked by two 5' purines and two 3' pyrimidines (12).…”

Systemic and in-situ natural killer activity in tumour-bearing rats

“…A role for the macrophage in the regulation of NK activity at a systemic level has been suggested (Oehler & Herberman, 1978) butwhetheranyrelationship exists at the tumour site is unknown. The appearance of various host-cell populations in tumours strongly suggests that the actual events in vivo are dependent upon precisely controlled relationships between the infiltrating cell types.…”

“…The appearance of various host-cell populations in tumours strongly suggests that the actual events in vivo are dependent upon precisely controlled relationships between the infiltrating cell types. Probably in no situation is this more apparent than the MSV tumour-host system, where the cytolytic activity of both intra-tumour T lymphocytes (fHolden et al, 1976;Gillespie et al, 1977;Plata & Sordat, 1977) and macrophages varies with the growth status of neoplasms. For instance, specifically cytotoxic T cells can be isolated from both regressors and progressors, but in the latter only during the early stages of tumour growth .…”