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Journal of Virology, March 2005, p. 3063-3070, Vol. 79, No. 5
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.5.3063-3070.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Anatomical and Cellular Requirements for the Activation and Migration of Virus-Specific CD8+ T Cells to the Brain during Theiler's Virus Infection

Yanice V. Mendez-Fernandez,1 Michael J. Hansen,1 Moses Rodriguez,1,2 and Larry R. Pease1*

Department of Immunology,1 Department of Neurology, Mayo Clinic College of Medicine, Rochester, Minnesota2

Received 4 June 2004/ Accepted 21 October 2004

Theiler's murine encephalomyelitis virus (TMEV) infection of the brain induces a virus-specific CD8+ T-cell response in genetically resistant mice. The peak of the immune response to the virus occurs 7 days after infection, with an immunodominant CD8+ T-cell response against a VP2-derived capsid peptide in the context of the Db molecule. The process of activation of antigen-specific T cells that migrate to the brain in the TMEV model has not been defined. The site of antigenic challenge in the TMEV model is directly into the brain parenchyma, a site that is considered immune privileged. We investigated the hypothesis that antiviral CD8+ T-cell responses are initiated in situ upon intracranial inoculation with TMEV. To determine whether a brain parenchymal antigen-presenting cell is responsible for the activation of virus-specific CD8+ T cells, we evaluated the CD8+ T-cell response to the VP2 peptide in bone marrow chimeras and mutant mice lacking peripheral lymphoid organs. The generation of the anti-TMEV CD8+ T-cell response in the brain requires priming by a bone marrow-derived antigen-presenting cell and the presence of peripheral lymphoid organs. Although our results show that activation of TMEV-specific CD8+ T cells occurs in the peripheral lymphoid compartment, they do not exclude the possibility that the immune response to TMEV is initiated by a brain-resident, bone marrow-derived, antigen-presenting cell.

* Corresponding author. Mailing address: Department of Immunology, Mayo Clinic College of Medicine, 200 First Ave. SW, Rochester, MN 55905. Phone: (507) 284-8177. Fax: (507) 266-0981. E-mail: pease.larry{at}mayo.edu.

Journal of Virology, March 2005, p. 3063-3070, Vol. 79, No. 5
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.5.3063-3070.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



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