Anatomical and cellular requirements for the activation and migration of virus-specific CD8+ T cells to the brain during Theiler's virus infection.
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 D(b) 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.
Mendez-Fernandez
Yanice V
YV
Department of Immunology, Mayo Clinic College of Medicine, 200 First Ave. SW, Rochester, MN 55905, USA.
Hansen
Michael J
MJ
Rodriguez
Moses
M
Pease
Larry R
LR
D000818:Animals; D017951:Antigen Presentation; D000938:Antigen-Presenting Cells / Q000276:immunology / Q000821:virology; D001854:Bone Marrow Cells / Q000276:immunology / Q000821:virology; D001921:Brain / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D036022:Capsid Proteins / Q000276:immunology; D018188:Cardiovirus Infections / Q000276:immunology*; D002465:Cell Movement; D008198:Lymph Nodes / Q000276:immunology; D008213:Lymphocyte Activation; D008221:Lymphoid Tissue / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D013154:Spleen / Q000276:immunology; D017945:Theilovirus / Q000276:immunology / Q000472:pathogenicity
D036022:Capsid Proteins; C442556:VP2 protein, Theilovirus