Patients with limbic encephalitis (LE) have brain structure inflammation. They also present with lymphoid cells and auto-antibodies. These patients are susceptible to spontaneous chronic seizures or temporal lobe epilepsy (TLE). This study assesses the role of distinct lymphocyte subsets in TLE and hippocampal sclerosis (HS).
The study focuses on CD8+ T-cells that target hippocampal neurons in mice. The CA1 neurons and model autoantigen Ovalbumin (OVA) are scrutinized. The pathogenic effects of their recombinant expression mediated by the adeno-associated virus are also under the study. The OVA-CD8+ LE model in OT-I/RAG1 mice is utilized for this purpose.
The dense CD8+ T‐cell infiltrates due to antigen transfer had a confined hippocampal formation on 5th day five after virus transduction. The flow cytometry showed CD8+ T‐cells priming in brain lymphatic before the hippocampal invasion. The acute model stage revealed inflammation, frequent seizures, and hippocampal memory impairment. The 7th-day MRI‐scans of the OVA‐CD8+ LE model presented hippocampal edema and blood‐brain‐barrier disruption leading to atrophy in 40 days. The CD8+ T‐cells had SIINFEKL‐H‐2Kb positive CA1 neurons, with OVA expression, as specific targets. It led to astrogliosis, segmental apoptotic neurodegeneration, and microglial activation. The chronic model stage mice had recurrent spontaneous seizures with memory deficit persistence. The CD8+ and NK-cells populated the sclerotic hippocampus.
The CD8+ T-cell initiates the distinct hippocampal neuron attack. It is sufficient for inducing LE leading to TLE-HS. These lymphocytes have a major pathogenic role that goes beyond neurotoxic effects in TLE after LE.