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Updated: Aug 18, 2026
Induction of Experimental Autoimmune Encephalomyelitis in Mice and Evaluation of the Disease-dependent Distribution of Immune Cells in Various Tissues
Published on: May 8, 2016
Neutralization of chemokines RANTES and MIG increases virus antigen expression and spinal cord pathology during
Daren R Ure1, Thomas E Lane, Michael T Liu
1Department of Neurology, Mayo Foundation and Graduate School, 428 Guggenheim Building, 201 1st Street SW, Rochester, MN 55905, USA.
Abstract:
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.
Insights
Blocking chemokines like RANTES and MIG during viral infections may worsen disease. This study shows these chemokines help control viral spread and limit immune-mediated damage in the central nervous system.
Area of Science:
- Neuroimmunology
- Virology
- Immunology
Background:
- Chemokines play a complex role in viral infections, potentially causing both immunity and tissue damage.
- Theiler's virus infection in SJL mice serves as a model for studying viral-induced central nervous system disease.
Purpose of the Study:
- To investigate the roles of regulated on activation, normal T cell-expressed and secreted (RANTES) and monokine induced by IFN-gamma (MIG) chemokines in Theiler's virus infection.
- To determine the impact of blocking these chemokines on viral persistence and immunopathology.
Main Methods:
- SJL mice were infected with Theiler's virus.
- Mice were treated with antisera against RANTES and MIG to block chemokine function.
- Viral antigen expression, inflammation, demyelination, and cytokine profiles (IL-2, IL-10) were assessed.
Main Results:
- Blocking RANTES or MIG increased viral antigen expression and demyelination severity.
- Viral load correlated with the extent of spinal cord pathology.
- RANTES antiserum treatment altered the IL-2/IL-10 ratio, indicating a shift in immune response.
Conclusions:
- RANTES and MIG are crucial for an immune response that controls viral replication and mitigates immunopathology.
- Blocking these chemokines can exacerbate viral infection and central nervous system damage.
- Targeting chemokines in viral infections requires careful consideration of potential long-term adverse effects.
