Experimental autoimmune encephalomyelitis (EAE) is a CD4+ T lymphocyte–mediated disease of the central nervous system (CNS) characterized by mononuclear cell infiltration, demyelination, and paralysis. We previously demonstrated a role for chemokines in acute and relapsing EAE pathogenesis. Presently, we investigated the role of CC chemokine receptor 2 (CCR2) in acute EAE. CCR2−/− mice did not develop clinical EAE or CNS histopathology, and showed a significant reduction in T cell– and CNS-infiltrating CD45highF4/80+ monocyte subpopulations. Peripheral lymphocytes from CCR2−/− mice produced comparable levels of interferon-gamma (IFN-γ) and interleukin (IL)-2 in response to antigen-specific restimulation when compared with control mice. Adoptively transferred myelin oligodendrocyte glycoprotein 35-55–specific T cells lacking expression of CCR2 were able to induce EAE, whereas CCR2−/− recipients of wild-type T cells failed to develop disease. These results suggest that CCR2 expression on host-derived mononuclear cells is critical for disease induction.
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18 September 2000
Brief Definitive Report|
September 18 2000
Cc Chemokine Receptor 2 Is Critical for Induction of Experimental Autoimmune Encephalomyelitis
Brian T. Fife,
Brian T. Fife
aDepartment of Pathology, Northwestern University Medical School, Chicago, Illinois 60611
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Gary B. Huffnagle,
Gary B. Huffnagle
bDepartment of Medicine, University of Michigan Medical School, Ann Arbor, Michigan 48109
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William A. Kuziel,
William A. Kuziel
cMolecular Genetics and Microbiology, University of Texas, Austin, Texas 78712
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William J. Karpus
William J. Karpus
aDepartment of Pathology, Northwestern University Medical School, Chicago, Illinois 60611
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Brian T. Fife
aDepartment of Pathology, Northwestern University Medical School, Chicago, Illinois 60611
Gary B. Huffnagle
bDepartment of Medicine, University of Michigan Medical School, Ann Arbor, Michigan 48109
William A. Kuziel
cMolecular Genetics and Microbiology, University of Texas, Austin, Texas 78712
William J. Karpus
aDepartment of Pathology, Northwestern University Medical School, Chicago, Illinois 60611
Received:
November 24 1999
Revision Requested:
August 01 2000
Accepted:
August 04 2000
Online ISSN: 1540-9538
Print ISSN: 0022-1007
© 2000 The Rockefeller University Press
2000
The Rockefeller University Press
J Exp Med (2000) 192 (6): 899–906.
Article history
Received:
November 24 1999
Revision Requested:
August 01 2000
Accepted:
August 04 2000
Citation
Brian T. Fife, Gary B. Huffnagle, William A. Kuziel, William J. Karpus; Cc Chemokine Receptor 2 Is Critical for Induction of Experimental Autoimmune Encephalomyelitis. J Exp Med 18 September 2000; 192 (6): 899–906. doi: https://doi.org/10.1084/jem.192.6.899
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