Induction of activation antigens on human natural killer cells mediated through the Fc-gamma receptor.
NK cells, defined here as lymphocytes bearing the CD16 Ag found on the NK cell Fc-gamma receptor (FcR), are known to enter a proliferative and activated state in response to stimulation with IL-2 as assessed by clonal expansion, short-term DNA synthesis, and de novo expression of lymphocyte-associated activation Ag. We have found that the FcR of NK cells acts as a signaling pathway through which IL-2-dependent activation may be greatly enhanced, allowing for more rapid induction of activation Ag and recruitment of an increased percentage of cells expressing surface markers of cellular activation. FcR-interactive agents, such as solid phase immobilized immune complexes or cross-linked CD16-specific mAb, work synergistically with rIL-2 to elicit a rapid expression of IL2R and transferrin receptors on greater than 50% of purified NK cells as early as day 3 of culture. IL-2 or FcR-interactive stimuli alone were weak or ineffective stimulators by comparison. In contrast to the induction of de novo activation Ag, DNA synthesis was elicited by IL-2 alone, but was not substantially or consistently enhanced by the subsequent addition of FcR-interactive stimuli.
Harris
D T
DT
Center for Environmental Medicine and Lung Biology, University of North Carolina, Chapel Hill 27599.
Travis
W W
WW
Koren
H S
HS
D000818:Animals; D000911:Antibodies, Monoclonal / Q000502:physiology; D000918:Antibody Specificity; D000936:Antigen-Antibody Complex / Q000502:physiology; D000943:Antigens, Differentiation / Q000096:biosynthesis* / Q000276:immunology / Q000502:physiology*; D002469:Cell Separation; D003432:Cross-Linking Reagents; D004247:DNA / Q000096:biosynthesis; D006801:Humans; D007074:Immunoglobulin G / Q000378:metabolism*; D007376:Interleukin-2 / Q000502:physiology; D007694:Killer Cells, Natural / Q000276:immunology / Q000378:metabolism*; D008213:Lymphocyte Activation; D051379:Mice; D011961:Receptors, Fc / Q000276:immunology / Q000502:physiology*; D017452:Receptors, IgG; D015375:Receptors, Interleukin-2 / Q000096:biosynthesis; D011990:Receptors, Transferrin / Q000096:biosynthesis; D014407:Tumor Cells, Cultured / Q000276:immunology / Q000378:metabolism
D000911:Antibodies, Monoclonal; D000936:Antigen-Antibody Complex; D000943:Antigens, Differentiation; D003432:Cross-Linking Reagents; D007074:Immunoglobulin G; D007376:Interleukin-2; D011961:Receptors, Fc; D017452:Receptors, IgG; D015375:Receptors, Interleukin-2; D011990:Receptors, Transferrin; D004247:DNA