title: Antibody response is required for protection from Theiler's virus-induced encephalitis in C57BL/6 mice in the absence of CD8+ T cells.
abstract: Intracerebral infection of susceptible mice with Theiler's murine encephalomyelitis virus (TMEV) induces immune-mediated demyelinating disease and this system serves as a relevant infectious model for human multiple sclerosis. It was previously shown that beta2M-deficient C57BL/6 mice lacking functional CD8+ T cells display increased viral persistence and enhanced susceptibility to TMEV-induced demyelination, and yet the majority of mice are free of clinical signs. To understand the mechanisms involved in this general resistance of C57BL/6 mice in the absence of CTL responses, mice (muMT) deficient in the B-cell compartment lacking membrane IgM molecules were treated with anti-CD8 antibody and then infected with TMEV. Although little difference in the proliferative responses of peripheral T cells to UV-inactivated TMEV and the resistance to demyelinating disease was observed between virus-infected muMT and control B6 mice, the levels of CD4(+) T cells were higher in the CNS of muMT mice. However, after treatment with anti-CD8 antibody, 100% of the mice displayed clinical gray matter disease and prolonged viral persistence in muMT mice, while only 10% of B6 mice showed clinical symptoms and very low viral persistence. Transfusion of sera from TMEV-infected B6 mice into anti-CD8 antibody-treated muMT mice partially restored resistance to virus-induced encephalitis. These results indicate that the early anti-viral antibody response is also important in the protection from TMEV-induced encephalitis particularly in the absence of CD8+ T cells.
authors.affiliation: Department of Microbiology-Immunology, Northwestern University, Medical School, Chicago, IL 60611, USA.
authors.forename: Bong-Su
authors.initials: BS
authors.lastname: Kang
authors.forename: Joann P
authors.initials: JP
authors.lastname: Palma
authors.forename: Michael A
authors.initials: MA
authors.lastname: Lyman
authors.forename: Mauro
authors.initials: M
authors.lastname: Dal Canto
authors.forename: Byung S
authors.initials: BS
authors.lastname: Kim
mesh_terms: D000818:Animals; D000917:Antibody Formation; D001402:B-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000382:microbiology; D018188:Cardiovirus Infections / Q000276:immunology*; D005434:Flow Cytometry; D006801:Humans; D007111:Immunity, Cellular / Q000276:immunology; D007153:Immunologic Deficiency Syndromes / Q000276:immunology / Q000821:virology; D051379:Mice; D008810:Mice, Inbred C57BL; D009103:Multiple Sclerosis / Q000276:immunology; D013154:Spleen / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology* / Q000821:virology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D017945:Theilovirus / Q000276:immunology*