To find immune mechanisms underlying relapse regulation, we developed a model of relapsing-remitting experimental autoimmune encephalomyelitis (EAE) in (B6xSJL) F1 (H-2 b / s ) mice by immunization with myelin oligodendrocyte glycoprotein peptide 35-55 (MOG 3 5 - 5 5 ) and compared with low/non-relapsing B6 (H-2 b ) mice.In relapsing H-2 b / s mice, inflammatory lesions scattered throughout the white matter with extensive demyelination, consisted of CD4 + T and B220 + B cells with fewer Mac3 + macrophages. Memory T cell proliferation to MOG 3 5 - 5 5 was significantly enhanced. Switch of macrophage chemoattractant protein-1 (MCP-1) production from GFAP + astrocytes to CD3 + T cells was observed.Distinct patterns of inflammation and demyelination, MOG 3 5 - 5 5 memory T cell response and regulation of MCP-1 are associated with relapsing H-2 b / s phenotype.