Recall Responses from Brain-Resident Memory CD8+ T Cells (bTRM) Induce Reactive Gliosis

Sujata Prasad, Shuxian Hu, Wen S Sheng, Priyanka Chauhan, James R Lokensgard

Research output: Contribution to journalArticlepeer-review

2 Scopus citations


HIV-associated neurocognitive disorders (HAND) persist even during effective combination antiretroviral therapy (cART). Although the cause of HAND is unknown, studies link chronic immune activation, neuroinflammation, and cerebrospinal fluid viral escape to disease progression. In this study, we tested the hypothesis that specific, recall immune responses from brain-resident memory T cells (bTRM) could activate glia and induce neurotoxic mediators. To address this question, we developed a heterologous prime-central nervous system (CNS) boost strategy in mice. We observed that the murine brain became populated with long-lived CD8+ bTRM, some being specific for an immunodominant Gag epitope. Recall stimulation using HIV-1 AI9 peptide administered in vivo resulted in microglia displaying elevated levels of major histocompatibility complex class II and programmed death-ligand 1, and demonstrating tissue-wide reactive gliosis. Immunostaining further confirmed this glial activation. Taken together, these results indicate that specific, adaptive recall responses from bTRM can induce reactive gliosis and production of neurotoxic mediators.

Original languageEnglish (US)
Pages (from-to)512-526
Number of pages15
StatePublished - Oct 25 2019

Bibliographical note

Funding Information:
This project was supported by award numbers NS-038836 from the National Institute of Neurological Disorders and Stroke and MH-066703 from the National Institute of Mental Health .

Publisher Copyright:
© 2019 The Author(s)

PubMed: MeSH publication types

  • Journal Article

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