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

Experimental autoimmune encephalomyelitis (EAE) is a CD4(+) T lymphocyte-me diated disease of the central nervous system (CNS) characterized by mononuc lear cell infiltration, demyelination, and paralysis. We previously demonst rated a role for chemokines in acute and relapsing EAE pathogenesis. Presen tly, we investigated the role of CC chemokine receptor 2 (CCR2) in acute EA E. CCR2(-/-) mice did not develop clinical EAE or CNS histopathology, and s howed a significant reduction in T cell- and CNS-infiltrating CD45(high)F4/ 80(+) monocyte subpopulations. Peripheral lymphocytes from CCR2(-/-) mice p roduced comparable levels of interferon-gamma (IFN-gamma) and interleukin ( IL)-2 in response to antigen-specific restimulation when compared with cont rol mice. Adoptively transferred myelin oligodendrocyte glycoprotein 35-55- specific T cells lacking expression of CCR2 were able to induce EAE, wherea s CCR2(-/-) recipients of wild-type T cells failed to develop disease. Thes e results suggest that CCR2 expression on host-derived mononuclear cells is critical for disease induction.