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

Mikkel L Hansen, Anders Woetmann, Thorbjørn Frej Krejsgaard, Katharina Luise Maria Kopp, Rolf Søkilde, Thomas Wojciech Zygmunt Litman, Per thor Straten, Carsten Geisler, Mariusz A Wasik, Niels Odum, Karsten Wessel Kam Eriksen

25 Citationer (Scopus)

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.
OriginalsprogEngelsk
TidsskriftMolecular Immunology
Vol/bind48
Udgave nummer15-16
Sider (fra-til)2087-93
Antal sider7
ISSN0161-5890
DOI
StatusUdgivet - 2011

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