Natural killer cells promote induction of experimental autoimmune encephalomyelitis but are protective at the acute stage of disease
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1
Trinity College Dublin, Trinity College School of Biochemistry and Immunology/ Trinity College Institute of Neuroscience, Ireland
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2
Trinity College Dublin, Trinity College School of Biochemistry and Immunology, Ireland
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3
Trinity College Dublin, Trinity College Institute of Neuroscience, Ireland
Experimental autoimmune encephalomyelitis (EAE) is a widely used animal model of multiple sclerosis and its induction is associated with the infiltration of encephalitogenic T cells into the CNS. Autoantigen-specific IL-17-producing Th17 cells and IFN-γ-producing Th1 cells are central to the pathogenesis of EAE. However, cells of the innate immune system, including γδ T cells and natural killer (NK) cells are also involved. Here we examined the role of NK cells in the induction and effector stages of EAE. Depletion of NK cells with anti-asialo GM1 at the induction of EAE led to a delayed onset of clinical signs with reduced disease severity. This correlated with a reduction in the numbers of Th1, Th17 and NKT cells infiltrating the CNS as well as a marked reduction in microglia in the CNS. In contrast, depletion of NK cells at onset of symptoms increased disease severity, while depletion at induction and throughout the course of EAE delayed the onset of clinical signs but enhanced disease severity once symptoms developed. We observed a similar pattern of delayed onset but more severe disease following induction of EAE in IFN-γ-/- mice (without NK cell depletion). These findings suggest that IFN-γ production by NK cells is involved in the induction of pathogenic immune responses that mediate EAE but is protective at the acute stage of disease, most likely by suppressing pathogenic Th17 cells.
Keywords:
Experimental autoimmune encephalomyelitis,
NK cells,
Microglia,
Mouse models of multiple sclerosis,
IFN- γ,
Autoimmunity
Conference:
15th International Congress of Immunology (ICI), Milan, Italy, 22 Aug - 27 Aug, 2013.
Presentation Type:
Abstract
Topic:
Immune-mediated disease pathogenesis
Citation:
Mc Guinness
N,
Dungan
LS,
Edwards
S,
Higgins
SC,
Lynch
MA and
Mills
KH
(2013). Natural killer cells promote induction of experimental autoimmune encephalomyelitis but are protective at the acute stage of disease.
Front. Immunol.
Conference Abstract:
15th International Congress of Immunology (ICI).
doi: 10.3389/conf.fimmu.2013.02.01158
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Received:
12 Jul 2013;
Published Online:
22 Aug 2013.
*
Correspondence:
Ms. Niamh Mc Guinness, Trinity College Dublin, Trinity College School of Biochemistry and Immunology/ Trinity College Institute of Neuroscience, Dublin, Ireland, mcguinni@tcd.ie