TY - JOUR

T1 - IFN-α primes T- and NK-cells for IL-15-mediated signaling and cytotoxicity

AU - Hansen, Mikkel L

AU - Woetmann, Anders

AU - Krejsgaard, Thorbjørn

AU - Kopp, Katharina L M

AU - Søkilde, Rolf

AU - Litman, Thomas

AU - Straten, Per T

AU - Geisler, Carsten

AU - Wasik, Mariusz A

AU - Ødum, Niels

AU - Eriksen, Karsten W

N1 - Copyright © 2011 Elsevier Ltd. All rights reserved.

PY - 2011/9

Y1 - 2011/9

N2 - 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.

AB - 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.

KW - Blotting, Western

KW - Cell Separation

KW - Cells, Cultured

KW - Cytotoxicity, Immunologic

KW - Flow Cytometry

KW - Humans

KW - Interferon-alpha

KW - Interleukin-15

KW - Killer Cells, Natural

KW - Lymphocyte Activation

KW - Lymphocyte Culture Test, Mixed

KW - Receptors, Interleukin-15

KW - Recombinant Proteins

KW - Signal Transduction

KW - T-Lymphocytes

U2 - 10.1016/j.molimm.2011.07.008

DO - 10.1016/j.molimm.2011.07.008

M3 - Journal article

C2 - 21813181

VL - 48

SP - 2087

EP - 2093

JO - Molecular Immunology

JF - Molecular Immunology

SN - 0161-5890

IS - 15-16

ER -