Allostatic load of immune cells in the spleen and brain of the Kcna1-null mouse model of temporal lobe epilepsy.

Abstract

Human temporal lobe epilepsy (TLE), particularly drug-resistant TLE, is associated with chronic peripheral immune activation. Here, we determined whether a similar association was detectable in a genetic mouse model of TLE with spontaneous recurrent seizures (SRS), Kcna1-null mice. Flow cytometry was used with fluorescence-activated cell sorting to determine the presence of lymphocytes, macrophages and granulocytes in isolated brain and spleen of wildtype (WT) and Kcna1-null mice. Splenic analysis revealed uniformly elevated Mac-1MHC-IImacrophages across all epileptic mice, whereas CD8cytotoxic T-cells increased proportionally with severe seizure frequency and burden, resulting in reduced CD4/CD8ratios-an immune risk phenotype. Brain tissue showed increased infiltration of both CD4and CD8T-cells. Importantly, Kv1.1 was not expressed on T-cells of WT mice. Using an allostatic interpretative framework, our results indicate that the immune system anticipates ongoing challenges (SRS) and maintains elevated readiness with an allostatic shift towards chronic adaptation (macrophages), but in doing so potentially damaging dynamic allostatic loads (CD8T-cells) are accumulated. The Kcna1-null model provides a valuable tool for investigating epilepsy immunopathogenesis without chemoconvulsant confounds. These findings support the notion that TLE has a significant immunological component which may participate in pathology and be a target for intervention.