Neuroprotective Effects of CD4+CD25+Foxp3+ Regulatory T Cells in a 3Xtg-Ad Alzheimer's Disease Model

Alzheimer's disease patients display neuropathological lesions, including the accumulation of amyloid-beta (Aβ) peptide and neurofibrillary tangles.Although the mechanisms causing the neurodegenerative process are largely unknown, increasing evidence highlights a critical role of immunity in the pathogenesis of Alzheimer's disease.In the present study, we investigated the role of regulatory T cells (Tregs) on Alzheimer's disease progression.First, we explored the effect of Tregs (CD4 + CD25 + T cells) and Teffs (CD4 + CD25 -T cells) in an 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 diminished behavioral function and cytokine production.Next, we transiently depleted Treg population using an anti-CD25 antibody (PC61).Depletion of Tregs for four months resulted in a marked aggravation of the spatial learning deficits of sixmonth-old 3xTg-AD mice.Additionally, it resulted in decreasing glucose metabolism, as assessed by positron emission tomography (PET) with 18 F-2 fluoro-2-deoxy-Dglucose ([F-18] FDG) neuroimaging.Importantly, the deposition of Aβ plaques and microglia/macrophage was increased in the hippocampal CA1 and CA3 regions of the Treg depleted 3xTg-AD compared to the vehicle-treated 3xTg-AD group.Our finding suggested that systemic Treg administration ameliorates disease progression and could be an effective Alzheimer's disease treatment.