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The Journal of Immunology, 2004, 173: 1514-1517.
Copyright © 2004 by The American Association of Immunologists

CUTTING EDGE

Cutting Edge: Innate Production of IFN-{gamma} by NK Cells Is Independent of Epigenetic Modification of the IFN-{gamma} Promoter1

Cristina M. Tato*, Gislâine A. Martins{dagger}, Frances A. High{dagger}, Catherine B. DiCioccio{dagger}, Steven L. Reiner{dagger} and Christopher A. Hunter2,*

* Department of Pathobiology, School of Veterinary Medicine and {dagger} Abramson Family Cancer Research Institute and Department of Medicine, University of Pennsylvania, Philadelphia, PA 19104

The ability of NK and T cells to produce IFN-{gamma} 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-{gamma} locus that allow them to produce IFN-{gamma}. The data presented here reveal that unlike T cells, murine NK cells produce IFN-{gamma} under conditions of short-term cytokine stimulation, and these events are independent of proliferation and cell cycle progression. Furthermore, analysis of the IFN-{gamma} locus in NK cells reveals that this locus is constitutively demethylated. The finding that NK cells do not need to remodel the IFN-{gamma} locus to produce IFN-{gamma}, 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.




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