Bystander CD8+ T cells are Important Antiviral Effectors in the Brain

Abstract The central nervous system (CNS) presents a unique immunological environment with restricted infiltration of immune cells from the periphery. Since much is unknown about CNS-infiltrating during infection, we utilized attenuated Venezuelan equine encephalitis virus vaccine strain TC83 (VEEV-TC83) to study T cell responses this viral infection. VEEV-TC83 intracranial (IC) infection wild-type mice produces high titers in brain without lethality, enabling complete antiviral response CNS. Many rapidly (5dpi) infiltrate CNS, seemingly antigen-independent manner, upon IC During CD8+ (~40% cells) express levels innate-memory markers. These bystander can produce IFNγ when treated IL-12 and IL-18, cytokines known induce innate signaling. IL-12, IL-15 (another supporter) are upregulated knockout (KO) results decreased CNS by cells. that do brains KO fewer activation markers cytokines, therefore likely not fully functional. Additionally, microglia support recruitment function Data deposited GEO indicate many neurotropic viruses induces Il15, Il12, Il18 expression tissues. Bystander an important first line defense Supported grants NIH (Training grant T32 AI07405 RO1 NS123431)