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Journal of Virology, September 2005, p. 11457-11466, Vol. 79, No. 17
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.17.11457-11466.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Neuronal CXCL10 Directs CD8⁺ T-Cell Recruitment and Control of West Nile Virus Encephalitis

Division of Infectious Diseases, Department of Medicine,¹ Departments of Pathology and Immunology,² Anatomy and Neurobiology,³ Molecular Microbiology, Washington University School of Medicine, St. Louis, Missouri 63110,⁴ Center for Immunology and Inflammatory Diseases, Division of Rheumatology, Allergy and Immunology, Massachusetts General Hospital, Charlestown, Massachusetts 02129⁵

Received 21 March 2005/ Accepted 28 May 2005

The activation and entry of antigen-specific CD8⁺ T cells into the central nervous system is an essential step towards clearance of West Nile virus (WNV) from infected neurons. The molecular signals responsible for the directed migration of virus-specific T cells and their cellular sources are presently unknown. Here we demonstrate that in response to WNV infection, neurons secrete the chemokine CXCL10, which recruits effector T cells via the chemokine receptor CXCR3. Neutralization or a genetic deficiency of CXCL10 leads to a decrease in CXCR3⁺ CD8⁺ T-cell trafficking, an increase in viral burden in the brain, and enhanced morbidity and mortality. These data support a new paradigm in chemokine neurobiology, as neurons are not generally considered to generate antiviral immune responses, and CXCL10 may represent a novel neuroprotective agent in response to WNV infection in the central nervous system.

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