Separation of human natural killer cell subpopulations differentially responsive to interferon potentiation

Subsets of human natural killer (NK) cells were identified that differed in the capacity to be activated by interferon (IFN) or the IFN-inducer, polyriboinosinic:polyribocytidylic acid [poly(I):poly(C)]. These subsets, which represented effectors of both spontaneous and antibody-dependent cellular cytotoxicity, were physically separable on the basis of cell buoyant density changes induced by exposure of lymphocytes to hyperosmolar Ficoll-Hypaque solutions or by centrifugation of lymphocytes through hyperosmolar (350 mOs/kg) Percoll gradients. Hyperosmolar conditions per se altered neither cell viability, NK cell cytolytic activity, nor the capacity of NK cells in unseparated lymphocyte preparations to be activated by IFN. IFN-unresponsive NK cells, separated by centrifugation through a 350 mOs/kg Percoll layer of 1.069-1.070 g/cm3 specific density, constituted 20 +/- 4% of all active NK cells identified at the single cell level and, per active NK cell, killed comparably to unstimulated IFN-responsive NK cells in 51Cr release assays. Thus, the IFN-unresponsive phenotype was probably not attributable to NK cells that were in an activated state prior to IFN treatment. Surface marker analysis of active NK cells at the single cell level identified comparable proportions in each subfraction to be of the OKM1+, OKT8+, or OKT11+ phenotypes and few, if any, in either subfraction to be of the OKT3+ phenotype. The human IFN-unresponsive NK cell phenotype, in contrast to the corresponding phenotype in the mouse, was therefore not linked to expression of T-cell-associated membrane differentiation antigens.