Endothelial cell MHC class I molecule restricted antigen presentation to CD8 T cells influences brain infiltration and establishment of antigen experienced T cell populations 3645

Abstract Description Brain Barrier (BBB) disruption plays a role in various neurodegenerative diseases such as ALS, stroke, Huntington’s disease and Cerebral Malaria. In our laboratory, we aim to interrogate the immunological underpinnings associated with neuroinflammation and barrier leakage. In clinical studies, aging is associated with a decline in T cell production and a gradual shift to resident memory T cells in the brain characterized by reduced T cell repertoire diversity and weak activation. To model these clinical observations, we sought to define the effect of MHC class I restricted antigen presentation on endothelial cells of brain vasculature on CD8 T cell infiltration of the CNS. We conditionally ablated H-2Kb and H-2Db molecules on endothelial cells using Cdh5-Cre mice crossed with our novel Kb LoxP and Db LoxP mice generated by our research program. In these animals we studied CD8 T cell accumulation in the brain using Theiler’s Murine Endothelial Virus (TMEV) infection of young mice (<12 months) compared to old mice (>12 months). Our results indicate that the loss of endothelial cell Kb induces a defect in establishment of antigen experienced CD8 T cell populations in acute infection. These finding will allow us to further investigate the role of endothelial cell MHC Class I molecules in the immune response to chronic TMEV infection, as well as other neurologic disease models. Funding Sources NIH Grants R01 NS103212 and R01 NS122174 Topic Categories Neuroimmunology (NEUR)