Natural killer (NK) cells are an early source of immunoregulatory cytokines during the innate immune response to viruses, bacteria, and parasites. NK cells provide requisite IFN-γ to monocytes for the elimination of obligate intracellular pathogens. IL-1β is a pro-inflammatory cytokine produced by monocytes (i.e. a monokine) during the early immune response to infection, but its role in promoting human NK cell IFN-γ production is unknown. The current study examines the ability of the monokine IL-1β, plus IL-12, to costimulate IFN-γ production by resting CD56bright and CD56dim human NK cell subsets. CD56bright NK cells stimulated with IL-1β plus IL-12 produced abundant IFN-γ protein, while little IFN-γ was produced in identical cultures of CD56dim cells. In addition, upon activation with IL-1β, CD56bright NK cells exhibited considerably greater phosphorylation of extracellular signal-regulated kinases p42/44 as compared to CD56dim NK cells. Quantitative PCR analysis showed brisk induction of IFN-γ gene expression following costimulation with IL-1β plus IL-12 in CD56bright NK cells, but intracellular flow cytometry revealed that only a fraction (42±2.3%) of CD56bright NK cells account for this high IFN-γ production. These data suggest that the monokine IL-1β is a potent costimulus of IFN-γ production by a subset of NK cells following infectious insult.
|Number of pages||10|
|Journal||European Journal of Immunology|
|State||Published - 2001|
- Innate immunity
- NK cell