Amyloid- β Specific Regulatory T Cells to Treat Alzheimer ' s Disease

T cells of the adaptive immune system do find their way into the brain to some degree, even given the existence of the blood-brain barrier that separates the brain from the vasculature. Researchers here report on an effort to engineer regulatory T cells to recognize amyloid-β, associated with the onset of Alzheimer's disease. In an animal model of Alzheimer's disease, mice engineered to generate amyloid-β aggregates, these engineered regulatory T cells reduced the resulting pathology by migrating into the brain and dampening the maladaptive inflammatory responses characteristic of neurodegenerative conditions. Regulatory T cells (Tregs) maintain immune tolerance. While Treg-mediated neuroprotective activities are now well-accepted, the lack of defined antigen specificity limits their therapeutic potential. This is notable for neurodegenerative diseases where cell access to injured brain regions is required for disease-specific therapeutic targeting and improved outcomes. To address this need, amyloid-beta (Aβ) antigen specificity was conferred to Treg responses by engineering the T cell receptor (TCR) specific for Aβ (TCRAβ). TCRAβ-Tregs were generated by CRISPR-Cas9 knockout of endogenous TCR and consequent incorporation of the transgenic TCRAb identified from Aβ reactive effector T cells. Adoptive transfer of TCRAβ-Tregs to mice expressing a chimeric mouse-human amyloid precursor protein and a mutant human presenilin-1 followed measured behavior, imm...
Source: Fight Aging! - Category: Research Authors: Tags: Daily News Source Type: blogs