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Journal of Virology, July 2002, p. 6577-6585, Vol. 76, No. 13
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.13.6577-6585.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

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

Bong-Su Kang, Michael A. Lyman, and Byung S. Kim*

Department of Microbiology-Immunology, Northwestern University Medical School, Chicago, Illinois 60611

Received 17 January 2002/ Accepted 3 April 2002

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 the H-2D major 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 (VP111-20 and VP3173-181) capsid protein epitopes. These virus-specific CD8+ T cells produce gamma interferon (IFN-{gamma}) 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-{gamma} 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-2Ks molecule, and this skewed class I restriction may be associated with susceptibility to demyelinating disease.

* Corresponding author. Mailing address: Department of Microbiology-Immunology, Northwestern University Medical School, 303 E. Chicago Ave., Chicago, IL 60611. Phone: (312) 503-8693. Fax: (312) 503-1339. E-mail: bskim{at}northwestern.edu.

Journal of Virology, July 2002, p. 6577-6585, Vol. 76, No. 13
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.13.6577-6585.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



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