J Immunol. 2004 Apr 1;172(7):4018-25
Glass WG, Hickey MJ, Hardison JL, Liu MT, Manning JE, Lane TE.
Center for Immunology and Department of Molecular Biology and Biochemistry, University of California, Irvine, CA 92697, USA.
Intracerebral infection of mice with mouse hepatitis virus, a member of the Coronaviridae family, reproducibly results in an acute encephalomyelitis that progresses to a chronic demyelinating disease.
The ensuing neuropathology during the chronic stage of disease is primarily immune mediated and similar to that of the human demyelinating disease multiple sclerosis.
Secretion of chemokines within the CNS signals the infiltration of leukocytes, which results in destruction of white matter and neurological impairment.
The CC chemokine ligand (CCL)5 is localized in white matter tracts undergoing demyelination, suggesting that this chemokine participates in the pathogenesis of disease by attracting inflammatory cells into the CNS.
In this study, we administer a mAb directed against CCL5 to mice with established mouse hepatitis virus-induced demyelination and impaired motor skills.
Anti-CCL5 treatment decreased T cell accumulation within the CNS based, in part, on viral Ag specificity, indicating the ability to differentially target select populations of T cells.
In addition, administration of anti-CCL5 improved neurological function and significantly (p < or = 0.005) reduced the severity of demyelination and macrophage accumulation within the CNS.
These results demonstrate that the severity of CNS disease can be reduced through the use of a neutralizing mAb directed against CCL5 in a viral model of demyelination.