Abeta-specific Th2 cells provide cognitive and pathological benefits to Alzheimer's mice without infiltrating the CNS

Neurobiol Dis. 2009 Apr;34(1):63-70. doi: 10.1016/j.nbd.2008.12.015. Epub 2009 Jan 8.

Abstract

We have found that a small number of purified Th2-biased Abeta-specific T cells are sufficient to provide profound cognitive and pathological benefits in an APP+PS1 mouse model for Alzheimer's disease. Six weeks after receiving T cell infusions, cognitively-impaired mice performed significantly better in working memory tasks, which correlated with higher plasma levels of soluble Abeta. Pathological analysis of the hippocampus revealed a 30% decrease of plaque-associated microglia and less vascular amyloidosis in T cell treated mice. The infusion of Abeta-specific Th2 cells also reduced plasma levels of IFN-gamma, TNF-alpha, GM-CSF, IL-2 and IL-4, which are elevated in untreated APP+PS1 mice. No significant immune cell infiltration and no anti-Abeta antibody titers occurred in the T cell treated mice. These results demonstrate that Abeta-specific Th2 cells are sufficient to reverse cognitive impairment and provide multiple pathological benefits in an Alzheimer's mouse model.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adoptive Transfer
  • Alzheimer Disease / physiopathology
  • Alzheimer Disease / therapy*
  • Amyloid beta-Peptides / blood
  • Amyloid beta-Peptides / immunology*
  • Amyloidosis / therapy
  • Animals
  • Cognition Disorders / physiopathology
  • Cognition Disorders / therapy
  • Disease Models, Animal
  • Granulocyte-Macrophage Colony-Stimulating Factor / blood
  • Hippocampus / physiopathology
  • Interferon-gamma / blood
  • Interleukin-2 / blood
  • Interleukin-4 / blood
  • Maze Learning / physiology
  • Memory Disorders / physiopathology
  • Memory Disorders / therapy
  • Mice
  • Mice, Transgenic
  • Microglia / physiology
  • Th2 Cells / immunology*
  • Th2 Cells / transplantation
  • Tumor Necrosis Factor-alpha / blood

Substances

  • Amyloid beta-Peptides
  • Interleukin-2
  • Tumor Necrosis Factor-alpha
  • Interleukin-4
  • Interferon-gamma
  • Granulocyte-Macrophage Colony-Stimulating Factor