In vitro NK-activity and in vivo resistance to leukemia: studies of beige, beige//nude and wild-type hosts on C57BL background

Abstract

The bg mutation in C57BL mice causes a partial impairment of NK activity, and has therefore been proposed as a model to evaluate the in vivo function of NK cells. In the present report, we studied natural resistance against the ascitic lines of one chemically and two virally induced syngeneic leukemias in C57BL bg/bg mice and their phenotypically normal heterozygous +/bg littermates. S.c. threshold inocula of all three leukemia lines grew faster and caused death earlier in bg/bg than in +/bg mice, and two of the lines were rejected completely at a significantly higher frequency in +/bg control animals. The +/bg mice also eliminated [125I]-IdUrd-labelled leukemia cells at a faster rate than bg/bg mice, as measured by pulmonary, hepatic and splenic radioactivity retained 18-30 h after i.v. injection. Direct splenic killing of 51Cr-labelled leukemia cells was also studied in vitro, and was found to be severely depressed in bg/bg compared to +/bg. This natural killer activity was independent of adherent cells and showed a rapid, but transient, increase after inoculation of the tumor cell doses used in the transplantation tests. It was also possible to study the bg mutation in T-cell-free mice, by combining it with the nu mutation on a C57BL background. The NK activity of such beige-nude mice was found to be partially impaired compared to nude (non-beige) or wild-type animals, but higher than that of beige (non-nude) mice. Our results suggest that NK cells may be responsible for elimination of small numbers of tumor cells in the intact syngeneic host. The further use of beige and beige-nude mice in studies of transplanted and primary tumors is discussed.