CD8+ T‐lymphocyte driven limbic encephalitis results in temporal lobe epilepsy

xloma.fota13 shared this article with you from Inoreader CD8+ T‐lymphocyte driven limbic encephalitis results in temporal lobe epilepsy Via Annals of Neurology Objective Limbic encephalitis (LE) comprises a spectrum of inflammatory changes in affected brain structures including the presence of autoantibodies and lymphoid cells. Still, the potential of distinct lymphocyte subsets alone to elicit key clinico‐pathological sequelae of LE potentially inducing temporal lobe epilepsy (TLE) with chronic spontaneous seizures and hippocampal sclerosis (HS) is unresolved. Methods Here, we scrutinized pathogenic consequences emerging from CD8+ T‐cells targeting hippocampal neurons by recombinant adeno‐associated virus‐mediated expression of the model‐autoantigen Ovalbumin (OVA) in CA1 neurons of OT‐I/RAG1‐/‐ mice (termed 'OVA‐CD8+ LE model'). Results Viral‐mediated antigen transfer caused dense CD8+ T‐cell infiltrates confined to the hippocampal formation starting on day five after virus transduction. Flow cytometry indicated priming of CD8+ T‐cells in brain‐draining lymph nodes to precede hippocampal invasion. At the acute model stage, the inflammatory process was accompanied by frequent seizure activity and impairment of hippocampal memory skills. MRI‐scans at day seven of the OVA‐CD8+ LE model revealed hippocampal edema and blood‐brain‐barrier disruption that converted into atrophy until day 40. CD8+ T‐cells specifically targeted OVA‐expressing, SIINFEKL‐H‐2Kb positive CA1 neurons and caused segmental apoptotic neurodegeneration, astrogliosis and microglial activation. At the chronic model stage, mice exhibited spontaneous recurrent seizures and persisting memory deficits, whilst the sclerotic hippocampus was populated with CD8+ T‐ce lls escorted by NK‐cells. Interpretation These data indicate that a CD8+ T‐cell initiated attack of distinct hippocampal neurons is sufficient to induce LE converting into TLE‐HS. Intriguingly, the role of CD8+ T‐cells exceeds neurotoxic effects and points to their major pathogenic role in TLE following LE. This article is protected by copyright. All rights reserved. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.