CC chemokine receptor 2 is critical for induction of experimental autoimmune encephalomyelitis

Brian T. Fife, Gary B. Huffnagle, William A. Kuziel, William J. Karpus

Research output: Contribution to journalArticlepeer-review

429 Scopus citations

Abstract

Experimental autoimmune encephalomyelitis (EAE) is a CD4+ T lymphocyte-mediated disease of the central nervous system (CNS) characterized by mononuclear cell infiltration, demy-elination, 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 CD45(high)F4/80+ 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.

Original languageEnglish (US)
Pages (from-to)899-905
Number of pages7
JournalJournal of Experimental Medicine
Volume192
Issue number6
DOIs
StatePublished - 2000

Keywords

  • CC chemokine receptor 2
  • CCL2
  • Experimental autoimmune encephalomyelitis
  • Knockout
  • Multiple sclerosis

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