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

Hansen, Mikkel L; Woetmann, Anders; Krejsgaard, Thorbjørn; Kopp, Katharina L M; Søkilde, Rolf LU ; Litman, Thomas; Straten, Per Th; Geisler, Carsten; Wasik, Mariusz A. and Odum, Niels, et al. (2011) In Molecular Immunology 48(15-16). p.93-2087
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... (More)

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.

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@article{6b93e609-ff90-402c-9bd1-f41b72d8c171,
  abstract     = {<p>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.</p>},
  author       = {Hansen, Mikkel L and Woetmann, Anders and Krejsgaard, Thorbjørn and Kopp, Katharina L M and Søkilde, Rolf and Litman, Thomas and Straten, Per Th and Geisler, Carsten and Wasik, Mariusz A. and Odum, Niels and Eriksen, Karsten W},
  issn         = {1872-9142},
  keyword      = {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},
  language     = {eng},
  number       = {15-16},
  pages        = {93--2087},
  publisher    = {Pergamon},
  series       = {Molecular Immunology},
  title        = {IFN-α primes T- and NK-cells for IL-15-mediated signaling and cytotoxicity},
  url          = {http://dx.doi.org/10.1016/j.molimm.2011.07.008},
  volume       = {48},
  year         = {2011},
}