Constitutive Cytokine mRNAs Mark Natural Killer (NK) and NK T Cells Poised for Rapid Effector Function

Abstract

Natural killer (NK) and NK T cells are tissue lymphocytes that secrete cytokines rapidly upon stimulation. Here, we show that these cells maintain distinct patterns of constitutive cytokine mRNAs. Unlike conventional T cells, NK T cells activate interleukin (IL)-4 and interferon (IFN)-γ transcription during thymic development and populate the periphery with both cytokine loci previously modified by histone acetylation. Similarly, NK cells transcribe and modify the IFN-γ gene, but not IL-4, during developmental maturation in the bone marrow. Lineage-specific patterns of cytokine transcripts predate infection and suggest evolutionary selection for invariant but distinct types of effector responses among the earliest responding lymphocytes.

CD1d-restricted iNKT cells, the ‘Swiss-Army knife’ of the immune system

“…How iNKT cells from unsensitized mice produce cytokines so rapidly when activated is unclear. However, the observation that resting iNKT cells have high levels of IL-4 and IFNγ mRNAs provides one potential mechanism [28,29]. Acquisition of this phenotype is a likely consequence of their unique mode of selection in the thymus, because CD4 T cells positively selected by MHC class-II expressed on thymocytes share similar effector functions [30].…”

“…Further studies will be required to understand the transcriptional regulation of cytokine production by iNKT cells. Epigenetic changes in chromatin structures at the IL-4 and IFNγ loci are known to occur during iNKT cell development in the thymus [29]. It was reported that Notch signaling might control the activity of an enhancer located downstream of the IL-4 locus that is responsible for the initial IL-4 expression in iNKT cells [45].…”

In vivo imaging of malaria parasites in the murine liver

“…Real-time in vivo imaging in the liver should also be valuable for visualizing anti-parasite immunity in context. The development of many mouse strains that produce fluorescent cell lines, such as myelomonocytic cells 21 , dendritic cells 22 or natural killer cells 23 , will help to dissect the role of these cell types during parasitic infection. Similar approaches should also permit illumination of how protective immunity is achieved and how activated T cells interact with infected hepatocytes, or comparison of immune effectors against parasites in naïve or vaccinated animals.…”

Sweet Is the Memory of Past Troubles: NK Cells Remember

“…One possible explanation is that activation with cytokines induces epigenetic changes at certain cytokine loci, similar to what has been described for memory induction and maintenance in T cells (Youngblood et al 2013). NK cells are already poised for rapid IFN-γ production with constitutive production of mRNA transcripts (Stetson et al 2003), so the question remains as to whether epigenetic modification at the Ifng locus would impact the generation of these memory-like NK cells. Epigenetic regulation could, however, provide a plausible explanation for why the progenies of the cytokine-activated NK cells also exhibit enhanced functions (Cooper et al 2009).…”