Recognition and regulation of progenitor marrow elements by NK cells in the mouse

Abstract

The cytotoxicity of radiolabelled YAC-1 target cells by natural killer (NK) cells from the spleens of immunocompetent CBA mice is inhibited by unlabelled YAC-1 competitor cells, but not by resting bone marrow from syngeneic or allogeneic adult mice. Rapidly proliferating haemopoietic cells recovered from the spleens of lethally irradiated, bone marrow-reconstituted CBA mice, however, compete strongly in the NK assay. The competitive ability of early regenerating marrow correlates with the presence of an increased percentage of morphologically immature cells of mixed lineages. Competition declines in reconstituted spleens recovered more than 10 days after engraftment, as the proportion of immature elements falls towards that of resting marrow. Although the numbers of unlabelled YAC-1 cells required to produce equivalent competition of unstimulated and interferon-activated NK killing are similar, 10 times fewer regenerating marrow competitors compete cytotoxicity by unstimulated NK effectors to the same degree as interferon activated cells. The numbers of granulocyte-macrophage colonies formed in soft agar by regenerating marrow is also influenced by prior incubation of the marrow cells with NK effector populations. Spleen cells from homozygous athymic mice produce the same effect as cells from their heterozygous littermates. These data suggest that NK cells recognize and regulate the differentiation of progenitor elements within the marrow.