Generation of Aβ-specific T cell lines and in vivo Transfer

Abstract

Amyloid-β (Aβ)-containing plaques accumulate in the brains of patients with Alzheimer’s disease (AD). Studies in transgenic mice which over-express amyloid precursor protein and presenilin 1 (APP/PS1 mice) have suggested that T cells that infiltrate the brain may influence the development of Aβ plaques and associated cognitive dysfuncation. Active immunization with Aβ peptides and adjuvants has been evaluated as a therapy for AD, based on the premise that it induces Aβ-specific antibodies that may help to clear the Aβ plaques. However, immunization with Aβ peptides and adjuvants also promotes the development of Aβ-specific T cells (McQuillan et al., 2010) and there is evidence that Aβ-specific T cell may influence the development of Aβ plaques and disease progression in AD patients. In the mouse model, Aβ-specific T cells that secrete IFN-γ (Th1 cells) have been shown to enhance the plaque burden (Browne et al., 2013). Adoptive transfer of Aβ-specific T cells that have been polarized in vitro to Th1, Th2, Th17 or Treg cells can be used to examine the function of these cells in vivo.