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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 orcid ; 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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publishing date
type
Contribution to journal
publication status
published
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
in
Molecular Immunology
volume
48
issue
15-16
pages
7 pages
publisher
Pergamon Press Ltd.
external identifiers
  • pmid:21813181
  • scopus:80051918473
ISSN
1872-9142
DOI
10.1016/j.molimm.2011.07.008
language
English
LU publication?
no
id
6b93e609-ff90-402c-9bd1-f41b72d8c171
date added to LUP
2017-09-01 14:30:40
date last changed
2024-06-09 22:48:40
@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}},
  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}},
  language     = {{eng}},
  number       = {{15-16}},
  pages        = {{93--2087}},
  publisher    = {{Pergamon Press Ltd.}},
  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}},
  doi          = {{10.1016/j.molimm.2011.07.008}},
  volume       = {{48}},
  year         = {{2011}},
}