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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.
Insights
Natural killer (NK) cells regulate hematopoietic progenitor differentiation. Immature marrow cells, not resting marrow, strongly compete in NK assays, indicating NK cell recognition of early progenitor elements.
Area of Science:
- Immunology
- Hematology
- Cell Biology
Background:
- Natural killer (NK) cells are crucial for innate immunity.
- NK cell activity is typically studied using tumor cell targets.
- The interaction of NK cells with hematopoietic progenitor cells is less understood.
Purpose of the Study:
- To investigate the interaction between NK cells and hematopoietic progenitor cells.
- To determine if NK cells can recognize and regulate early hematopoietic progenitor elements.
- To explore the role of NK cells in bone marrow regeneration.
Main Methods:
- Cytotoxicity assays using radiolabelled YAC-1 target cells and NK cells from CBA mice.
- Competition assays with unlabelled YAC-1 cells, resting bone marrow, and regenerating bone marrow.
- Analysis of morphologically immature cells in regenerating bone marrow.
- Colony formation assays for granulocyte-macrophage progenitors.
- Experiments using spleen cells from athymic mice.
Main Results:
- Unlabelled YAC-1 cells inhibited NK cell cytotoxicity, but resting bone marrow did not.
- Rapidly proliferating hematopoietic cells from regenerating bone marrow strongly competed in NK assays.
- Competitive ability correlated with the percentage of immature, mixed-lineage cells.
- NK cell activity influenced granulocyte-macrophage colony formation.
- NK cells from athymic mice showed similar effects to those from heterozygous littermates.
Conclusions:
- NK cells recognize and can regulate the differentiation of progenitor elements within the bone marrow.
- Regenerating bone marrow contains targets for NK cells, suggesting a role in immune surveillance of hematopoiesis.
- NK cells may play a role in controlling the proliferation and differentiation of early hematopoietic cells.