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T-Lymphocyte Driven Limbic Encephalitis Mouse Model: Differentiation of Inflammatory Cells for Tailored Therapies

Maria Kyriazi1, Julika Pitsch1, Katarzyna Placek2, Albert Becker1

1 Section for Translational Epilepsy Research, Department of Neuropathology, University of Bonn Medical Center, Bonn, Germany
2 Immunology and Metabolism, Life and Medical Sciences Institute, University of Bonn, Bonn, Germany

T-Lymphocyte Driven Limbic Encephalitis Mouse Model: Differentiation of Inflammatory Cells for Tailored Therapies

Maria Kyriazi, Julika Pitsch, Katarzyna Placek, Albert Becker

1Section for Translational Epilepsy Research, Department of Neuropathology, University of Bonn Medical Center, Bonn, Germany

2Immunology and Metabolism, Life and Medical Sciences Institute, University of Bonn, Bonn, Germany

Only recently, transient inflammation of the hippocampus and further parts of the limbic system (limbic encephalitis; LE) have been increasingly recognized as cause of temporal lobe epilepsy (TLE). Recent data provide new insights into the etiology of LE describing autoantibodies and the concomitant T-lymphocytes response as major factors. Prominent admixtures of T lymphocytes and seizures in several inflammatory and neurodegenerative disorders underscore the need for an improved understanding of “T lymphocyte to neuronal” signaling in the context of focal epilepsy. Several T lymphocyte subpopulations can interact with neurons by a plethora of cytokines or cytotoxic molecules.We will analyze the spectrum of CD8+T lymphocytes and released inflammatory mediators in LE crucial for the emergence of TLE. Therefore, we will make use of a LE mouse model specifically targeting hippocampal neurons. To this end, we breed OT-I-Rag1-/-mice that exclusively possess OVA-specific CD8+T cells and inject them with the rAAV virus carrying the OVA gene under control of neuron-specific promoter. After the stereotaxic transfer of a construct into the hippocampi CD8+T cell driven LE is induced. CD8+T cells will be characterized in the acute phase of epileptogenesis according to their cytotoxic potential, cytokine production, activation status and expression of homing markers by flow cytometry. Whereas in the chronic phase innate immune cells are found to be recruited, which will also be examind. Most prevalent inflammatory cell populations will be analyzed for their transcriptomic signature in order to translate the findings into therapeutic targets to reduce LE-mediated seizures.