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 β2M-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 (μMT) 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 μMT and control B6 mice, the levels of CD4+ T cells were higher in the CNS of μMT mice. However, after treatment with anti-CD8 antibody, 100% of the mice displayed clinical gray matter disease and prolonged viral persistence in μMT 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 μMT 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.
Original language | English (US) |
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Pages (from-to) | 84-94 |
Number of pages | 11 |
Journal | Virology |
Volume | 340 |
Issue number | 1 |
DOIs | |
State | Published - Sep 15 2005 |
Funding
This work was supported by United States Public Health Service Grants, RO1 NS28752, RO1 NS33008, and PO1 NS23349, and a grant from the National Multiple Sclerosis Society (RG 3126-A4).
Keywords
- Antibody
- CD8 T cells
- Encephalitis
- Protection
- Theiler's virus
ASJC Scopus subject areas
- Virology