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Regulatory T cells delay disease progression in Alzheimer-like pathology

Cira Dansokho, Dylla Ait Ahmed, Saba Aid, Cécile Toly-Ndour, Thomas Chaigneau, Vanessa Calle, Nicolas Cagnard, Martin Holzenberger, Eliane Piaggio, Pierre Aucouturier, Guillaume Dorothée
DOI: http://dx.doi.org/10.1093/brain/awv408 awv408 First published online: 1 February 2016

Summary

Recent studies highlight the implication of innate and adaptive immunity in the pathophysiology of Alzheimer’s disease, and foster immunotherapy as a promising strategy for its treatment. Vaccines targeting amyloid-β peptide provided encouraging results in mouse models, but severe side effects attributed to T cell responses in the first clinical trial AN1792 underlined the need for better understanding adaptive immunity in Alzheimer’s disease. We previously showed that regulatory T cells critically control amyloid-β-specific CD4+ T cell responses in both physiological and pathological settings. Here, we analysed the impact of regulatory T cells on spontaneous disease progression in a murine model of Alzheimer’s disease. Early transient depletion of regulatory T cells accelerated the onset of cognitive deficits in APPPS1 mice, without altering amyloid-β deposition. Earlier cognitive impairment correlated with reduced recruitment of microglia towards amyloid deposits and altered disease-related gene expression profile. Conversely, amplification of regulatory T cells through peripheral low-dose IL-2 treatment increased numbers of plaque-associated microglia, and restored cognitive functions in APPPS1 mice. These data suggest that regulatory T cells play a beneficial role in the pathophysiology of Alzheimer’s disease, by slowing disease progression and modulating microglial response to amyloid-β deposition. Our study highlights the therapeutic potential of repurposed IL-2 for innovative immunotherapy based on modulation of regulatory T cells in Alzheimer’s disease.

  • Alzheimer’s disease
  • regulatory T cells
  • microglia
  • immunotherapy
  • Abbreviations
    IFN
    interferon
    Teffs
    effector T cells
    Tregs
    regulatory T cells
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