A Role of CC Chemokines on the Pathogenesis of Herpes Simplex Encephalomyelitis

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Th1/Th2 responses play an important role on the host defense against herpes simplex encephalomyelitis. Recently, some specific chemokines have been described as an initiator of Th1/Th2 responses. We investigated a role of monocyte chemoattractant protein (MCP)-1 in the pathogenesis of herpesvirus-induced encephalomyelitis (HSM). Anti-MCP-1 antibody greatly decreased HSM severity in mice infected with herpes simplex virus type 2 (HSM mice). HSM severity was markedly enhanced in mice previously treated with a mixture of interleukin (IL) 4 and -10. In response to stimulation with antigen, HSM mouse cells isolated from cerebrospinal fluids (CSF cells) produced IL-4 in culture fluids, however, IL-4 production decreased in CSF cells derived from HSM mice previously treated with anti-MCP-1 antibody. A macrophage population isolated in CSF cells from HSM mice (CSF-Mphi) produced MCP-1 in culture fluids. In response to stimulation with herpesvirus antigen, T cells isolated from CSF cells from HSM mice (CSF-T cells) produced IL-4 into their culture fluids, although MCP-1 was not produced by CSF-T cells. IL-4 production by CSF-T cells was markedly enhanced when they were stimulated with viral antigen in the presence of murine recombinant MCP-1 (rMCP-1). Furthermore, IL-4 was produced in naive splenic T cells cocultured with CSF-Mphi. These results indicate that the severity of HSM is influenced by MCP-1, which stimulates Th2 responses.