Resistance to experimental autoimmune encephalomyelitis in mice lacking the CC chemokine receptor (CCR)2

Monocyte recruitment to the central nervous system (CNS) is a necessary ste p in the development of pathologic inflammatory lesions in experimental aut oimmune encephalomyelitis (EAE), a murine model of multiple sclerosis. Mono cyte chemoattractant protein (MCP)-1, a potent agonist for directed monocyt e migration, has been implicated in the pathogenesis of EAE. Here we report that deficiency in CC chemokine receptor (CCR)2, the receptor for MCP-1, c onfers resistance to EAE. induced with a peptide derived from myelin oligod endrocyte glycoprotein peptide 35-55 (MOGp35-55). CCR2(-/-) mice immunized with MOGp35-55 failed to develop mononuclear cell inflammatory infiltrates in the CNS and failed to increase CNS levels of the chemokines RANTES (regu lated on activation, normal T cell expressed and secreted), MCP-1, and inte rferon (IFN)-inducible protein 10 (IP-10) as well the chemokine receptors C CR1, CCR2, and CCR5. Additionally, T cells from CCR2(-/-) immunized mice sh owed decreased antigen-induced proliferation and production of IFN-gamma co mpared with wild-type immunized controls, suggesting that CCR2 enhances the T helper cell type 1 immune response in EAE. These data indicate that CCR2 Flays a necessary and nonredundant role in the pathogenesis of EAE.