Open AccessNeuronal CXCL10 Directs CD8 + T-Cell Recruitment and Control of West Nile Virus Encephalitis
Author(s) -
Robyn S. Klein,
Eugene C. Lin,
Bo Zhang,
Andrew D. Luster,
Judy Tollett,
Melanie A. Samuel,
Michael J. Engle,
Michael S. Diamond
Publication year - 2005
Publication title -
journal of virology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.617
H-Index - 292
eISSN - 1070-6321
pISSN - 0022-538X
DOI - 10.1128/jvi.79.17.11457-11466.2005
Subject(s) - biology , cxcr3 , cxcl10 , cytotoxic t cell , chemokine , virology , cd8 , chemokine receptor , immune system , virus , t cell , immunology , genetics , in vitro
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.