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Re-analysis of astrocyte-enriched single-cell sequencing from bacterial mimetic-injected mice revealed a transcriptionally distinct interferon-responsive astrocyte population enriched for antigen-presentation-associated genes 24 hours after peripheral immune challenge. In vivo, we identify MHC-II+GFAP+ astrocytes localized to the surface of the brain across multiple mouse models of neuroinflammation and in human neurological disease tissue. In a pure in vitro culture system, astrocytes stimulated with IFN\u03b3 and proinflammatory cytokines express MHC-II, costimulatory molecules and lymphocyte-recruiting chemokines, and support rapid antigen-dependent expansion of previously activated CD4+ T cells. Using human iPSC-derived CNS cultures, we additionally show induction of antigen-presentation-associated machinery in human astrocytes following inflammatory cytokine stimulation. Rather than inferring function solely from marker expression, we assessed astrocyte-supported T cell restimulation in vitro and separately characterized the emergence of antigen-presentation-associated astrocytes in vivo at neuroimmune interfaces during inflammation in mice and humans. 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