Interleukin 3 is a major negative regulator of the generation of natural killer cells from bone marrow precursors.
We have established a bone marrow culture system in which mature natural killer (NK) cells can be generated from inactive precursors by interleukin 2. Recombinant interleukin 3 (IL 3) almost completely blocked the induction of NK cells in this culture system as judged by cytotoxic activity, as well as appearance of cells with NK phenotype. The dose-response curve for inhibition of the generation of NK activity with IL 3 parallelled the growth promoting activity on the strictly IL 3-dependent cell line L/B. The effect of IL 3 was selective for the precursor stage of the NK cell, because mature NK cells were not affected by culture with IL 3 for the same period of time. Moreover, the effect of IL 3 was confined to the first 24 hr of culture, indicating an effect on an early stage of NK cell differentiation. IL 3 did not increase the small normally occurring NK-sensitive population in bone marrow, and did not affect the activity of a variant cytotoxic cell with specificity for adherent target cells, the natural cytotoxic cell. Concomitantly with downregulation of NK cell generation, IL 3 induced strong proliferation in the bone marrow cultures and an increase in the percentage of cells expressing the T cell marker Thy-1. A model for regulation of NK cells based on competition of growth factors for target cells with a common progenitor is discussed.
D000818:Animals; D000954:Antigens, Surface / Q000032:analysis; D001854:Bone Marrow Cells; D002454:Cell Differentiation / Q000187:drug effects; D003602:Cytotoxicity, Immunologic; D005677:G(M1) Ganglioside; D006028:Glycosphingolipids / Q000032:analysis; D007376:Interleukin-2 / Q000494:pharmacology; D007377:Interleukin-3 / Q000502:physiology*; D007694:Killer Cells, Natural / Q000166:cytology* / Q000276:immunology; D051379:Mice; D013154:Spleen / Q000166:cytology; D013491:Suppressor Factors, Immunologic; D018800:Thy-1 Antigens
D000954:Antigens, Surface; D006028:Glycosphingolipids; D007376:Interleukin-2; D007377:Interleukin-3; D013491:Suppressor Factors, Immunologic; D018800:Thy-1 Antigens; D005677:G(M1) Ganglioside; C018835:asialo GM1 ganglioside