title: IFN-α primes T- and NK-cells for IL-15-mediated signaling and cytotoxicity.
abstract: Recently it has become clear that interferon (IFN)-α, a type I interferon produced rapidly in response to infection, not only plays a key role in innate immunity, but also promotes adaptive immune responses by influencing the production or function of other cytokines. During infections IFN-α fosters the production of IL-15, which plays a pivotal role in the development, survival and function of NK cells and recruitment and activation of T cells. Since these two cytokines exert overlapping functions during infections, this investigation was undertaken to study the priming effect of IFN-α on the effect of IL-15 on human T and NK cells. We show that IFN-α induces an increased expression of IL-15Rα in human activated peripheral T cells, and in CD8(+) and CD4(+) T-cell lines. Functionally, the IFN-α-enhanced IL-15Rα expression resulted in an enhanced IL-15-mediated phosphorylation of STAT5 and STAT3 followed by a further increase in IL-15Rα expression. Moreover, IFN-α significantly increased the IL-15-induced cytotoxic activity of freshly isolated T and NK cells. Taken together, our data show that IFN-α boosts signaling and functional effects of IL-15, at least in part by fostering the increased IL-15R expression, thus add new facet to the emerging role of IFN-α as an important primer of adaptive immune responses.
authors.affiliation: Department of International Health, Immunology and Microbiology, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Mikkel L
authors.initials: ML
authors.lastname: Hansen
authors.forename: Anders
authors.initials: A
authors.lastname: Woetmann
authors.forename: Thorbjørn
authors.initials: T
authors.lastname: Krejsgaard
authors.forename: Katharina L M
authors.initials: KL
authors.lastname: Kopp
authors.forename: Rolf
authors.initials: R
authors.lastname: Søkilde
authors.forename: Thomas
authors.initials: T
authors.lastname: Litman
authors.forename: Per T
authors.initials: PT
authors.lastname: Straten
authors.forename: Carsten
authors.initials: C
authors.lastname: Geisler
authors.forename: Mariusz A
authors.initials: MA
authors.lastname: Wasik
authors.forename: Niels
authors.initials: N
authors.lastname: Odum
authors.forename: Karsten W
authors.initials: KW
authors.lastname: Eriksen
mesh_terms: D015153:Blotting, Western; D002469:Cell Separation; D002478:Cells, Cultured; D003602:Cytotoxicity, Immunologic / Q000276:immunology; D005434:Flow Cytometry; D006801:Humans; D016898:Interferon-alpha / Q000276:immunology* / Q000378:metabolism; D019409:Interleukin-15 / Q000276:immunology* / Q000378:metabolism; D007694:Killer Cells, Natural / Q000276:immunology* / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology*; D007959:Lymphocyte Culture Test, Mixed; D053647:Receptors, Interleukin-15 / Q000276:immunology / Q000378:metabolism; D011994:Recombinant Proteins / Q000276:immunology / Q000378:metabolism; D015398:Signal Transduction / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism
chemical_list: D016898:Interferon-alpha; D019409:Interleukin-15; D053647:Receptors, Interleukin-15; D011994:Recombinant Proteins