Natural killer (NK) cells as a responder to interleukin 2 (IL 2). I. Proliferative response and establishment of cloned cells.
The proliferative response of murine natural killer (NK) cells to a T cell growth factor, interleukin 2 (IL 2) was investigated by using the NK-enriched, low-density fractions (F.1) and NK-depleted, T cell-enriched, and high-density fractions (F.3) of normal spleen cells after Percoll-discontinuous density gradient centrifugation. When F.1 and F.3 cells were cultivated with IL 2-containing medium without addition of any other factors, like lectins, feeder layer, or macrophage products, F.1 but not F.3 cells showed an IL 2-dependent proliferative response. Growing populations showed a potent NK activity and consisted largely of cells with a morphology of large granular lymphocyte (LGL) and a surface marker profile characteristic for murine NK cells. By limiting dilution in the liquid culture and colony formation in the soft agar medium, F.1 but not F.3 cells showed a high frequency of clonal replication in IL 2. Almost all growing colonies in either medium showed a typical morphology of LGL. Further, F.1 cells treated with anti-asialo GM1 antibody and C, from which NK cells and cytolytic activity were almost completely abrogated and for which T cells were enriched, conversely formed a few IL 2-dependent colonies. From the colonies in soft agar, 11 clones, all of which showed a typical morphology (LGL), a typical surface profile with the exception of lacking IgG-Fc receptors for NK cells (Thy-1 +/-, Ly-5+, ASGM1+, Lyt-1-, Lyt-2-, Fc gamma R-), and a cytotoxic activity of activated nature, were established and maintained for a period of longer than 1 yr in the medium containing IL 2 alone. These results indicate that a major population in the naive spleens of normal mice that respond directly to IL 2 and clonally replicate without other stimulating factors may be NK cells.
D000818:Animals; D000920:Antibody-Dependent Cell Cytotoxicity; D000954:Antigens, Surface / Q000032:analysis; D002469:Cell Separation; D002499:Centrifugation, Density Gradient; D002999:Clone Cells / Q000166:cytology / Q000276:immunology; D003470:Culture Media; D007376:Interleukin-2 / Q000494:pharmacology*; D007694:Killer Cells, Natural / Q000166:cytology / Q000276:immunology*; D008213:Lymphocyte Activation; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D010641:Phenotype; D051381:Rats; D011919:Rats, Inbred Strains; D013601:T-Lymphocytes / Q000276:immunology
D000954:Antigens, Surface; D003470:Culture Media; D007376:Interleukin-2