Antibody Targeting of the CC Chemokine Ligand 5 Results in Diminished Leukocyte Infiltration into the Central Nervous System and Reduced Neurologic Disease in a Viral Model of Multiple Sclerosis

• Published in: The Journal of immunology (1950) 2004-04, Vol.172 (7), p.4018-4025
• Main Authors: Glass, William G, Hickey, Michelle J, Hardison, Jenny L, Liu, Michael T, Manning, Jerry E, Lane, Thomas E
• Format: Article
• Language: English
• Subjects: Animals; Antibodies, Monoclonal - administration & dosage; Antibodies, Monoclonal - therapeutic use; CCL5 protein; Cell Migration Inhibition; Central Nervous System - immunology; Central Nervous System - pathology; Central Nervous System - virology; Chemokine CCL5 - antagonists & inhibitors; Chemokine CCL5 - biosynthesis; Chemokine CCL5 - genetics; Chemokine CCL5 - immunology; Chemokines, CC - immunology; Chemokines, CC - metabolism; Chemotaxis, Leukocyte - immunology; Coronavirus Infections - immunology; Coronavirus Infections - pathology; Coronavirus Infections - therapy; Demyelinating Diseases - immunology; Demyelinating Diseases - pathology; Demyelinating Diseases - prevention & control; Disease Models, Animal; Encephalomyelitis - immunology; Encephalomyelitis - pathology; Encephalomyelitis - therapy; Injections, Intraperitoneal; leukocytes; Ligands; Macrophage Activation - immunology; Macrophages - immunology; Macrophages - pathology; Mice; Mice, Inbred C57BL; Multiple Sclerosis - immunology; Multiple Sclerosis - pathology; Multiple Sclerosis - prevention & control; Murine hepatitis virus; Murine hepatitis virus - immunology; RNA, Messenger - antagonists & inhibitors; RNA, Messenger - biosynthesis; Severity of Illness Index; T-Lymphocyte Subsets - immunology; T-Lymphocyte Subsets - pathology; T-Lymphocyte Subsets - virology
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.172.7.4018

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.