CC chemokine receptor 2 is critical for induction of experimental autoimmune encephalomyelitis.
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 CD45(high)F4/80(+) monocyte subpopulations. Peripheral lymphocytes from CCR2(-/-) mice produced comparable levels of interferon-gamma (IFN-gamma) 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.
Fife
B T
BT
Department of Pathology, Northwestern University Medical School, Chicago, Illinois 60611, USA.
Huffnagle
G B
GB
Kuziel
W A
WA
Karpus
W J
WJ
D000595:Amino Acid Sequence; D000818:Animals; D002478:Cells, Cultured; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology*; D007371:Interferon-gamma / Q000096:biosynthesis; D007376:Interleukin-2 / Q000096:biosynthesis; D008213:Lymphocyte Activation; D008214:Lymphocytes / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein / Q000737:chemistry / Q000276:immunology; D063308:Myelin-Oligodendrocyte Glycoprotein; D009836:Oligodendroglia / Q000276:immunology; D010446:Peptide Fragments / Q000276:immunology; D054390:Receptors, CCR2; D019707:Receptors, Chemokine / Q000172:deficiency / Q000235:genetics / Q000276:immunology*; D012016:Reference Values; D020133:Reverse Transcriptase Polymerase Chain Reaction
C515335:Ccr2 protein, mouse; D007376:Interleukin-2; C571327:Mog protein, mouse; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein; D063308:Myelin-Oligodendrocyte Glycoprotein; D010446:Peptide Fragments; D054390:Receptors, CCR2; D019707:Receptors, Chemokine; D007371:Interferon-gamma