MHC class I expression by microglia is required for generating a complete antigen-specific CD8 T cell response in the CNS

Identification: Malo, Courtney


Description

 

MHC class I expression by microglia is required for generating a complete antigen-specific CD8 T cell response in the CNS
 
Courtney S. Malo1,2, Fang Jin1, Michael J. Hansen1, John D. Fryer3, Kevin D. Pavelko1, Aaron J. Johnson1,3,4
1Department of Immunology, Mayo Clinic; 2Mayo Clinic Graduate School of Biomedical Sciences, Mayo Clinic, 3Department of Neurology, Mayo Clinic; 1Department of Molecular Medicine, Mayo Clinic
      
Microglia are central nervous system (CNS) resident immune cells for which the impact of MHC class I antigen presentation is still being defined. To directly address the extent to which microglia contribute to CD8 T cell-mediated immunity of the CNS, we generated a novel tamoxifen inducible CX3CR1-creER H-2Kb MHC class I conditional knockout mouse on an H-2Db-deficient background. In this transgenic mouse, the H-2Kb MHC class I molecule is deleted on all CX3CR1-expressing cells following tamoxifen treatment. By two weeks post tamoxifen treatment, peripheral CX3CR1-expressing cells repopulate, restoring normal expressing of H-2Kb. This leaves only microglia as the sole MHC class I-deficient cell type. We hypothesized that deletion of H-2Kb on microglia would impair CD8 T cell responses in the CNS. We challenged these animals and cre-negative littermates with intracranial picornavirus infection with Theiler's murine encephalomyelitis virus expressing ovalbumin (TMEV-OVA). We determined that microglia-specific H-2Kb deletion reduces the CD8 T cell response in the CNS. Furthermore, this reduction is primarily found in the Kb:OVA antigen-specific CD8 T cell compartment. We conclude that microglia are functional antigen presenting cells, and are required for a complete antigen-specific CD8 T cell response in the brain. These findings demonstrate a critical role for microglia-expressed MHC class I in neuroinflammation.
 

 

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