Resistance to Experimental Autoimmune Encephalomyelitis in Mice Lacking the CC Chemokine Receptor (CCR)2

doi:10.1084/jem.192.7.1075

Published online 2 October 2000.

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© The Rockefeller University Press, 0022-1007/2000/10/1075/ $5.00
The Journal of Experimental Medicine, Volume 192, Number 7, October 2, 2000 1075-1080

Brief Definitive Report

Resistance to Experimental Autoimmune Encephalomyelitis in Mice Lacking the CC Chemokine Receptor (CCR)2

Leonid Izikson^a, Robyn S. Klein^b, Israel F. Charo^c, Howard L. Weiner^a, and Andrew D. Luster^b
^a Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115
^b Center for Immunology and Inflammatory Diseases, Division of Rheumatology, Allergy, and Immunology, Massachussetts General Hospital, Harvard Medical School, Boston, Massachusetts 02114
^c Gladstone Institute, University of California at San Francisco, San Francisco, California 94141

Correspondence to: Andrew D. Luster, Massachusetts General Hospital-East, Bldg. 149 13th St., Charlestown, MA 02129. Tel:617-726-5710 Fax:617-726-5651

Monocyte recruitment to the central nervous system (CNS) isa necessary step in the development of pathologic inflammatorylesions in experimental autoimmune encephalomyelitis (EAE),a murine model of multiple sclerosis. Monocyte chemoattractantprotein (MCP)-1, a potent agonist for directed monocyte migration,has been implicated in the pathogenesis of EAE. Here we reportthat deficiency in CC chemokine receptor (CCR)2, the receptorfor MCP-1, confers resistance to EAE induced with a peptidederived from myelin oligodendrocyte glycoprotein peptide 35–55(MOGp35–55). CCR2^-/- mice immunized with MOGp35–55failed to develop mononuclear cell inflammatory infiltratesin the CNS and failed to increase CNS levels of the chemokinesRANTES (regulated on activation, normal T cell expressed andsecreted), MCP-1, and interferon (IFN)-inducible protein 10(IP-10) as well the chemokine receptors CCR1, CCR2, and CCR5.Additionally, T cells from CCR2^-/- immunized mice showed decreasedantigen-induced proliferation and production of IFN- ${gamma}$ comparedwith wild-type immunized controls, suggesting that CCR2 enhancesthe T helper cell type 1 immune response in EAE. These dataindicate that CCR2 plays a necessary and nonredundant role inthe pathogenesis of EAE.

Key Words: receptors, chemokine, chemokines, macrophages, encephalomyelitis,cytokines

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