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, Michael J. Hansen, Moses Rodriguez, Larry R. Pease

Research output: Contribution to journalArticlepeer-review

19 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)3063-3070
Number of pages8
JournalJournal of virology
Volume79
Issue number5
DOIs
StatePublished - Mar 2005

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

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