Monocyte chemoattractant protein-1 enhances HSV-induced encephalomyelitis by stimulating Th2 responses.
Monocyte chemoattractant protein (MCP)-1 has a pathogenic role in herpesvirus-induced encephalomyelitis (HSM). Anti-MCP-1 antibody greatly decreased HSM severity in mice infected with herpes simplex virus type 2 (HSM mice), compared with its effect in control HSM mice treated with rabbit immunoglobulin. 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, a population of 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 stimulated by this antigen. 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.
Nakajima
H
H
Division of Infectious Diseases, Department of Internal Medicine, The University of Texas Medical Branch, Galveston 77555-0435, USA.
Kobayashi
M
M
Pollard
R B
RB
Suzuki
F
F
D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D002478:Cells, Cultured; D002555:Cerebrospinal Fluid / Q000276:immunology; D018932:Chemokine CCL2 / Q000276:immunology / Q000494:pharmacology / Q000502:physiology*; D002522:Chlorocebus aethiops; D004679:Encephalomyelitis / Q000134:cerebrospinal fluid / Q000276:immunology* / Q000821:virology*; D006561:Herpes Simplex / Q000134:cerebrospinal fluid / Q000276:immunology*; D018258:Herpesvirus 2, Human / Q000472:pathogenicity*; D015847:Interleukin-4 / Q000096:biosynthesis; D007700:Kinetics; D008264:Macrophages / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D015996:Survival Rate; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology*; D014709:Vero Cells
D000906:Antibodies; D018932:Chemokine CCL2; D015847:Interleukin-4