Genetic control of in vitro NK-activity and in vivo resistance to tumors.
Natural Killer (NK) cells are lymphocyte like cells which lack conventional B- and T-cell characteristics, and have the ability to rapidly kill certain tumor cells in vitro. Analysis of the genetic control of NK-activity in mice have provided several models to test the in vivo role of NK-cells in defence against neoplasia. Studies of certain F1-hybrid and backcross combinations have revealed a correlation between H-2 linked in vivo resistance and in vitro NK-activity against semisyngeneic transplantable tumors. The beige (bg) mutation in C57B1 mice causes a partial impairment of NK-activity, and can therefore serve to evaluate whether NK-cells can contribute to resistance against syngeneic tumors in the normal intact host. We have recently studied natural resistance against the ascitic lines of one chemically and two virally induced syngeneic leukemias in C57B1.bg/bg mice and their phenotypically normal heterozygous 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 14-30 h after i.v. injection. The bg mutation was also possible to study in T-cell free mice, by combining it with the nu mutation on a C57B1 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, autochthonous tumors will be discussed.
D000818:Animals; D005796:Genes; D006183:H-2 Antigens / Q000235:genetics; D007694:Killer Cells, Natural / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL / Q000235:genetics; D008811:Mice, Inbred DBA / Q000235:genetics; D008817:Mice, Mutant Strains / Q000235:genetics; D008819:Mice, Nude / Q000235:genetics; D009154:Mutation; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000276:immunology*; D013045:Species Specificity
D006183:H-2 Antigens