Infiltrating CD8+ T cells exacerbate Alzheimer's disease pathology in a novel 3D human neuroimmune axis model

T cells have been proposed to play a role in Alzheimer’s disease (AD) pathology by infiltrating the brain and interacting with resident cells. Here, we describe a novel three- dimensional (3D) human neuroimmune axis model comprised of human stem cell-derived neurons, astrocytes, and microglia, together with human peripheral immune cells. We used this neuroimmune axis model to examine the infiltration of peripheral immune cells into AD versus control neural-glial cell cultures. Using single-cell RNA- sequencing, we identified that infiltrating T cells into AD cultures led to induction of interferon-gamma and neuroinflammatory-associated pathways in microglial cells. To compare T cell mediated glial actvation various conditions such as 3D culture (Neuron/astrocyte), 3D triculture (Neuron/Astrocyte/Microglia), 3D PiChip (Neuron/Astrocyte/Microglia/T cells), and 3D culture with T cells (Neuron/Astrocyte/T cells) in CTRL and AD prepared accoding to the timeline and isolated from central chamber (brain compartment) for the Droplet-based single cell RNAseq.