Microglia and Perivascular Macrophages Act as Antigen Presenting Cells to Promote CD8 T Cell Infiltration of the Brain

Emma N. Goddery, Cori E. Fain, Chloe G. Lipovsky, Katayoun Ayasoufi, Lila T. Yokanovich, Courtney S. Malo, Roman H. Khadka, Zachariah P. Tritz, Fang Jin, Michael J. Hansen, Aaron J. Johnson

Research output: Contribution to journalArticlepeer-review

Abstract

CD8 T cell infiltration of the central nervous system (CNS) is necessary for host protection but contributes to neuropathology. Antigen presenting cells (APCs) situated at CNS borders are thought to mediate T cell entry into the parenchyma during neuroinflammation. The identity of the CNS-resident APC that presents antigen via major histocompatibility complex (MHC) class I to CD8 T cells is unknown. Herein, we characterize MHC class I expression in the naïve and virally infected brain and identify microglia and macrophages (CNS-myeloid cells) as APCs that upregulate H-2Kb and H-2Db upon infection. Conditional ablation of H-2Kb and H-2Db from CNS-myeloid cells allowed us to determine that antigen presentation via H-2Db, but not H-2Kb, was required for CNS immune infiltration during Theiler’s murine encephalomyelitis virus (TMEV) infection and drives brain atrophy as a consequence of infection. These results demonstrate that CNS-myeloid cells are key APCs mediating CD8 T cell brain infiltration.

Original languageEnglish (US)
Article number726421
JournalFrontiers in immunology
Volume12
DOIs
StatePublished - Aug 30 2021

Keywords

  • antigen presentation
  • atrophy
  • CD8 T cell
  • MHC class I
  • microglia
  • perivascular macrophage
  • TMEV
  • viral infection

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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