Update on T cells in the virally infected brain: friends and foes

Abstract

Purpose of review: The present review will outline neuroprotective and neurotoxic effects of central nervous system (CNS) infiltrating T cells during viral infections. Evidence demonstrating differential roles for antiviral effector and resident memory T-cell subsets in virologic control and immunopathology in the CNS will be discussed. Potential therapeutic targets emanating from a growing understanding of T-cell-initiated neuropathology that impacts learning and memory will also be delineated.

Recent findings: The critical role for T cells in preventing and clearing CNS infections became incontrovertible during the era of acquired immunodeficiency syndrome. Recent studies have further defined differential roles of T-cell subsets, including resident memory T cells (Trm), in antiviral immunity and, unexpectedly, in postinfectious cognitive dysfunction. Mechanisms of T-cell-mediated effects include differential innate immune signaling within neural cells that are virus-specific.

Summary: T-cell cytokines that are essential for cell-mediated virologic control during neurotropic viral infections have recently been identified as potential targets to prevent post-infection memory disorders. Further identification of T-cell subsets, their antigen specificity, and postinfection localization of Trm will enhance the efficacy of immunotherapies through minimization of immunopathology.

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FIGURE 1

Mechanisms underlying neurological sequelae in survivors of WNV and ZIKV encephalitis. (1) Infiltrating antiviral, effector, IFNγ-expressing CD8 T cells promote virolgic clearance from infected neurons. (2) Trm-derived IFNγ, which remains chronically elevated, promotes microglial activation, and subsequent engulfment of presynaptic (WNV) or postsynaptic (ZIKV) termini in the CA3 region of the hippocampus and deficits in spatial learning [^▪▪]. The figure is based on a figure in the journal 10.1038/nature18283.