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

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.

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.

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.