Cutting Edge: Innate Production of IFN-γ by NK Cells Is Independent of Epigenetic Modification of the IFN-γ Promoter

Abstract

The ability of NK and T cells to produce IFN-γ is critical for resistance to numerous intracellular pathogens but the kinetics of these responses differ. Consistent with this is a requirement for naive T cells to become activated and undergo proliferation-dependent epigenetic changes to the IFN-γ locus that allow them to produce IFN-γ. The data presented here reveal that unlike T cells, murine NK cells produce IFN-γ under conditions of short-term cytokine stimulation, and these events are independent of proliferation and cell cycle progression. Furthermore, analysis of the IFN-γ locus in NK cells reveals that this locus is constitutively demethylated. The finding that NK cells do not need to remodel the IFN-γ locus to produce IFN-γ, either because they do not exhibit epigenetic repression or they have undergone prior remodeling during development, provides a molecular basis for the innate and adaptive regulation of the production of this cytokine.