Neuromodulatory activities of CD4+CD25+Foxp3+ regulatory T cells in 3xTg-AD Alzheimer’s disease model

Abstract

Abstract Alzheimer’s disease (AD) is the most prevalent cause of dementia marked by progressive cognitive and functional impairment and memory loss. AD patients display neuropathological lesions including deposition of extracellular amyloid-beta (Aβ) peptide and the formation of neurofibrillary tangles. Although the mechanisms causing brain atrophy and neuronal death are largely unknown, increasing evidence suggests that immunity plays a critical role in the pathogenesis of AD. In the present study, we investigated the effect of regulatory T cells (Tregs) on AD mouse model. First, we transiently depleted Treg population using anti-CD25 antibody. Depletion of Tregs for 4 months resulted in a marked aggravation of the spatial learning deficits of 6-month-old 3xTg-AD mice. Importantly, deposition of Aβ plaques and CD11b+ microglia/macrophage were significantly increased in the hippocampal CA1 and CA3 regions of the Treg depleted 3xTg-AD compared to the vehicle-treated 3xTg-AD group. Next, we explored the effect of Teffs (effector T cells; CD4+CD25−) and Treg (CD4+CD25+) in adoptive transfer model. Systemic transplantation of purified Tregs into 3xTg-AD mice improved cognitive function and reduced deposition of Aβ plaques. In contrast, adoptive transfer of Teffs showed increased Aβ plaques burden and diminished behavioral function. Our finding strongly suggested that systemic Treg administration ameliorates disease progression and could be an effective AD treatment.