MHC Class I deletion on pericytes alters lymphocyte infiltration during Theiler’s murine encephalomyelitis virus 2198

Abstract Description CD8 T cell induced blood-brain barrier (BBB) disruption is an established mechanism of neuropathology. The pericyte is a MHC class I expressing neurovascular unit cell type which is critical for maintaining BBB integrity. However, the importance of pericyte antigen-restricted engagement by CD8 T cells is not fully understood. To determine the function of pericyte MHC Class I antigen presentation, we crossed the Pdgfrβ-creERT2 mouse to our novel H-2Db LoxP mouse developed by our laboratory. This transgenic mouse approach enabled us to target pericytes during neuroinflammation. We observed robust knockdown of H-2Db on Pdgfrβ+ pericytes during TMEV infection in these animals. The effect of conditional H-2Db knockdown on this cell type resulted in increased CD4 T cell, CD8 T cell, and B cells infiltration of the brain during TMEV infection, demonstrating an important role of Pdgfrβ+ pericytes for immune cell recruitment into the CNS. To our knowledge, this is the first study demonstrating an important role for MHC class I antigen presentation by pericytes in a murine model of neuroinflammation. Funding Sources Supported by R01NS122174 and R01NS103212 Topic Categories Neuroimmunology (NEUR)