CC Chemokine Receptor 2 Is Critical for Induction of Experimental Autoimmune

doi:10.1084/jem.192.6.899

Published online 18 September 2000.

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© The Rockefeller University Press, 0022-1007/2000/9/899/ $5.00
The Journal of Experimental Medicine, Volume 192, Number 6, September 18, 2000 899-906

Brief Definitive Reports

CC Chemokine Receptor 2 Is Critical for Induction of Experimental Autoimmune Encephalomyelitis

Brian T. Fife^a, Gary B. Huffnagle^b, William A. Kuziel^c, and William J. Karpus^a
^a Department of Pathology, Northwestern University Medical School, Chicago, Illinois 60611
^b Department of Medicine, University of Michigan Medical School, Ann Arbor, Michigan 48109
^c Molecular Genetics and Microbiology, University of Texas, Austin, Texas 78712

Correspondence to: William J. Karpus, Department of Pathology, Northwestern University Medical School, 303 E. Chicago Ave., W127, Chicago, IL 60611. Tel:312-503-1005 Fax:312-503-1217

Experimental autoimmune encephalomyelitis (EAE) is a CD4⁺ Tlymphocyte–mediated disease of the central nervous system(CNS) characterized by mononuclear cell infiltration, demyelination,and paralysis. We previously demonstrated a role for chemokinesin acute and relapsing EAE pathogenesis. Presently, we investigatedthe role of CC chemokine receptor 2 (CCR2) in acute EAE. CCR2^-/-mice did not develop clinical EAE or CNS histopathology, andshowed a significant reduction in T cell– and CNS-infiltratingCD45^highF4/80⁺ monocyte subpopulations. Peripheral lymphocytesfrom CCR2^-/- mice produced comparable levels of interferon-gamma(IFN- ${gamma}$ ) and interleukin (IL)-2 in response to antigen-specificrestimulation when compared with control mice. Adoptively transferredmyelin oligodendrocyte glycoprotein 35-55–specific T cellslacking expression of CCR2 were able to induce EAE, whereasCCR2^-/- recipients of wild-type T cells failed to develop disease.These results suggest that CCR2 expression on host-derived mononuclearcells is critical for disease induction.

Key Words: multiple sclerosis, experimental autoimmune encephalomyelitis,CC chemokine receptor 2, knockout, CCL2

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