Theiler's virus is eliminated by a gamma-interferon-independent mechanism in the brain.
The intravenous infection of Theiler's virus GD VII strain causes acute encephalomyelitis in infected mice. To determine the cellular mechanism of resistance and interferon (IFN)-gamma-producing cell populations, mononuclear cells isolated from tissues of the brain were analyzed by the flow cytometry method. Antibodies specific for CD3, CD4, CD8, T cell receptor (TCR)-alpha beta, and Asialo GM1 were used to deplete the corresponding cell populations in Theiler's virus-infected mice. CD4+ lymphocytes and CD8+ lymphocytes infiltrated in the brains of infected mice from 5 days postinfection (p.i.). The number of CD3+/TCR-gamma delta+ lymphocytes increased in the brains on Day 6 p.i. The elimination of CD3+ lymphocytes or CD4+ lymphocytes augmented viral replication and suppressed the production of IFN-gamma. The suppression of IFN-gamma production by anti-CD3 monoclonal antibody (mAb) persisted, although the suppression by anti-CD4 mAb was observed only on Day 6 p.i. The depletion of CD8+ lymphocytes as well as TCR-alpha beta+ lymphocytes also augmented the viral replication; however, it did not alter the production of IFN-gamma. Anti-Asialo GM1 antibody had no effect on viral replication and IFN-gamma production. These results indicate that T lymphocytes are important for eliminating Theiler's virus from the brain, CD3+/CD4+/CD8- lymphocytes and CD3+/TCR alpha beta-/CD4-/CD8- lymphocytes would produce IFN-gamma in brain. However, from the result on the experiment of the depletion of TCR-alpha beta+ lymphocytes, the defence mechanisms by T lymphocytes against Theiler's virus would be independent of endogenous IFN-gamma production.
Kohanawa
M
M
Department of Microbiology, Hokkaido University School of Medicine, Sapporo, Japan.
Nakane
A
A
Asano
M
M
Minagawa
T
T
D000818:Animals; D015703:Antigens, CD / Q000032:analysis; D001921:Brain / Q000276:immunology* / Q000382:microbiology; D005260:Female; D007371:Interferon-gamma / Q000502:physiology*; D051379:Mice; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000032:analysis; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000032:analysis; D013601:T-Lymphocytes / Q000502:physiology*; D017945:Theilovirus / Q000276:immunology*; D014779:Virus Replication
D015703:Antigens, CD; D016693:Receptors, Antigen, T-Cell, alpha-beta; D016692:Receptors, Antigen, T-Cell, gamma-delta; D007371:Interferon-gamma