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.
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.
Funder
National Institute of Neurological Disorders and Stroke
Subject
Immunology,Immunology and Allergy
Cited by
49 articles.
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