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

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

JOURNAL=Frontiers in Immunology

VOLUME=12

YEAR=2021

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2021.726421

DOI=10.3389/fimmu.2021.726421

ISSN=1664-3224

ABSTRACT=<p>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 <italic>via</italic> 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-2K<sup>b</sup> and H-2D<sup>b</sup> upon infection. Conditional ablation of H-2K<sup>b</sup> and H-2D<sup>b</sup> from CNS-myeloid cells allowed us to determine that antigen presentation <italic>via</italic> H-2D<sup>b</sup>, but not H-2K<sup>b</sup>, 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.</p>