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International Immunology Advance Access originally published online on April 11, 2005
International Immunology 2005 17(5):569-579; doi:10.1093/intimm/dxh236
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© The Japanese Society for Immunology. 2005. All rights reserved. For permissions, please e-mail: journals.permissions@oupjournals.org

Neutralization of chemokines RANTES and MIG increases virus antigen expression and spinal cord pathology during Theiler's virus infection

Daren R. Ure1,4, Thomas E. Lane2, Michael T. Liu2 and Moses Rodriguez1,3

1 Department of Immunology and 3 Department of Neurology, Mayo Foundation and Graduate School, 428 Guggenheim Building, 201 1st Street SW, Rochester, MN 55905 USA
2 Center for Immunology and Department of Molecular Biology and Biochemistry, University of California, Irvine, CA 92612-3900, USA
4 Present address: Isotechnika, Inc., 5120, 75th Street, Edmonton, Alberta T6E 6W2 Canada

Correspondence to: M. Rodriguez; E-mail: rodriguez.moses{at}mayo.edu

The role of chemokines during some viral infections is unpredictable because the inflammatory response regulated by these molecules can have two, contrasting effects—viral immunity and immunopathologic injury to host tissues. Using Theiler's virus infection of SJL mice as a model of this type of disease, we have investigated the roles of two chemokines—regulated on activation, normal T cell-expressed and secreted (RANTES) chemokine and monokine induced by IFN-{gamma} (MIG)—by treating mice with antisera that block lymphocyte migration. Control, infected mice showed virus persistence, mild inflammation and a small degree of demyelination in the white matter of the spinal cord at 6 weeks post-infection. Treatment of mice with RANTES antiserum starting at 2 weeks post-infection increased both viral antigen expression and the severity of inflammatory demyelination at 6 weeks post-infection. MIG antiserum increased the spread of virus and the proportion of spinal cord white matter with demyelination. Overall, viral antigen levels correlated strongly with the extent of pathology. At the RNA level, high virus expression was associated with low IL-2 and high IL-10 levels, and RANTES antiserum decreased the IL-2/IL-10 ratio. Our results suggest that RANTES and MIG participate in an immune response that attempts to restrict viral expression while limiting immunopathology and that anti-chemokine treatment poses the risk of exacerbating both conditions in the long term.

Keywords: chemokines, demyelination, interleukins, virus persistence

Transmitting editor: M. Miyasaka


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