Short-term CD8+ T cells ablation reduces microgliosis in the hippocampus of old APP/PS1 animals

Alzheimer´s disease (AD) progression has been recently associated to the infiltration of CD8+ T cells into disease-affected brain parenchyma, where they tightly associate with microglial and neuronal structures. However, the functional role of CD8+ T cells in the AD brain is still elusive. Therefore, we investigated the impact of short-term CD8+ T cell ablation on neuroinflammation in transgenic AD mice (APP/PS1).CD8+ T cells ablation was performed via intraperitoneal injections of anti-CD8 antibody for three days in two-year-old APP/PS1 and wild-type male mice. Control groups received the respective isotype antibody (four animals per group). Heart-collected blood samples underwent flow cytometry (FC) analysis. After transcardiac perfusion, the brain tissue was processed for immunohistochemistry staining and RNA isolation for gene expression analysis.As expected anti-CD8 injections resulted in a substantial decrease of CD8+ T cells from the blood circulation as well as brain parenchyma. Although amyloid plaque pathology and dystrophic neurite distribution were unchanged upon anti-CD8 treatment, we observed a statistically significant reduction in the percentage area of Iba1+ cells in the hippocampus of APP/PS1 mice treated with anti-CD8 antibody compared to isotype-treated mice. Quantitative PCR analysis of the cortex and hippocampus did not reveal anti-CD8-dependent changes in the expression of neuronal immediate early genes (Arc, Npsa4) and neuroinflammatory markers (Il1b, H2Aa).Short-term CD8+ T cell ablation revealed a consistent reduction of microglial cell staining area in the hippocampus of treated animals. These results suggest that short-term CD8 ablation could influence microglia-driven neuroinflammation.