The Majority of Infiltrating CD8+T Cells in the Central Nervous System of Susceptible SJL/J Mice Infected with Theiler's Virus Are Virus Specific and Fully Functional
Open Access
- 1 July 2002
- journal article
- Published by American Society for Microbiology in Journal of Virology
- Vol. 76 (13) , 6577-6585
- https://doi.org/10.1128/jvi.76.13.6577-6585.2002
Abstract
Theiler's virus infection of the central nervous system (CNS) induces an immune-mediated demyelinating disease in susceptible mouse strains, such as SJL/J, and serves as a relevant infectious model for human multiple sclerosis. It has been previously suggested that susceptible SJL/J mice do not mount an efficient cytotoxic T-lymphocyte (CTL) response to the virus. In addition, genetic studies have shown that resistance to Theiler's virus-induced demyelinating disease is linked to theH-2Dmajor histocompatibility complex class I locus, suggesting that a compromised CTL response may contribute to the susceptibility of SJL/J mice. Here we show that SJL/J mice do, in fact, generate a CD8+T-cell response in the CNS that is directed against one dominant (VP3159-166) and two subdominant (VP111-20and VP3173-181) capsid protein epitopes. These virus-specific CD8+T cells produce gamma interferon (IFN-γ) and lyse target cells in the presence of the epitope peptides, indicating that these CNS-infiltrating CD8+T cells are fully functional effector cells. Intracellular IFN-γ staining analysis indicates that greater than 50% of CNS-infiltrating CD8+T cells are specific for these viral epitopes at 7 days postinfection. Therefore, the susceptibility of SJL/J mice is not due to the lack of an early functional Theiler's murine encephalomyelitis virus-specific CTL response. Interestingly, T-cell responses to all three epitopes are restricted by the H-2Ksmolecule, and this skewed class I restriction may be associated with susceptibility to demyelinating disease.Keywords
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