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. 2002 Nov 11;52(1):79–86. doi: 10.1016/0165-5728(94)90165-1

Theiler's virus is eliminated by a gamma-interferon-independent mechanism in the brain

Masashi Kohanawa 1,∗, Akio Nakane 1, Misako Asano 1, Tomonori Minagawa 1
PMCID: PMC7119829  PMID: 8207121

Abstract

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)-γ-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)-αβ, 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-γδ+ 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-γ. The suppression of IFN-γ 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-αβ+ lymphocytes also augmented the viral replication; however, it did not alter the production of IFN-γ. Anti-Asialo GM1 antibody had no effect on viral replication and IFN-γ production. These results indicate that T lymphocytes are important for eliminating Theiler's virus from the brain, CD3+/CD4+/CD8− lymphocytes and CD3+/TCRαβ−/CD4−/CD8− lymphocytes would produce IFN-γ in brain. However, from the result on the experiment of the depletion of TCR-αβ+ lymphocytes, the defence mechanisms by T lymphocytes against Theiler's virus would be independent of endogenous IFN-γ production.

Keywords: Theiler's virus, T lymphocytes, Endogenous interferon-γ, Acute encephalomyelitis

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