Natural cytotoxicity in AKR/J mice during adjuvant induced amyloidogenesis☆

Abstract The induction of amyloidosis in AKR mice has previously been shown to be associated with a decrease in the incidence of spontaneous thymic leukemia (P. Ebbesen, Brit. J. Cancer 29 , 76, 1974). Amyloid induction with azocasein depresses the activity of the natural killer (NK) cell, a cell believed to be important in the protection against the development of malignancy. In the present studies, therefore, we examined the response of the NK cell to the induction of amyloidosis in AKR mice. Rapid and long-term depression of NK cell activity against YAC-1 tumor cells was noted following intraperitoneal administration of complete Freund's adjuvant enriched with Mycobacterium butyricum . Mixing studies suggested that active suppression did not account for the observed decrease in NK cell activity. Although some NK cell activity was noted in ascitic fluid, redirection was not felt to account for the rapid and dramatic reduction in splenic NK cell activity. Furthermore, serum from adjuvant-treated but not control mice was found to significantly inhibit NK cell activity in vitro . These studies therefore suggested a role for a serum factor in the depression of this activity. The apparent paradox of decreased NK cell activity in a setting of diminished leukemogenesis is considered in relation to previous studies describing impaired T-cell functioning after the induction of amloidosis.