IFN-α primes T- and NK-cells for IL-15-mediated signaling and cytotoxicity

Research output: Contribution to journalArticle

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.

Details

Authors
  • Mikkel L Hansen
  • Anders Woetmann
  • Thorbjørn Krejsgaard
  • Katharina L M Kopp
  • Rolf Søkilde
  • Thomas Litman
  • Per Th Straten
  • Carsten Geisler
  • Mariusz A. Wasik
  • Niels Odum
  • Karsten W Eriksen
External organisations
  • Exiqon AS
Research areas and keywords

Keywords

  • Blotting, Western, Cell Separation, Cells, Cultured, Cytotoxicity, Immunologic, Flow Cytometry, Humans, Interferon-alpha, Interleukin-15, Killer Cells, Natural, Lymphocyte Activation, Lymphocyte Culture Test, Mixed, Receptors, Interleukin-15, Recombinant Proteins, Signal Transduction, T-Lymphocytes, Journal Article, Research Support, Non-U.S. Gov't
Original languageEnglish
Pages (from-to)2087-93
Number of pages7
JournalMolecular Immunology
Volume48
Issue number15-16
Publication statusPublished - 2011 Sep
Publication categoryResearch
Peer-reviewedYes
Externally publishedYes