Journal
NEUROBIOLOGY OF DISEASE
Volume 34, Issue 1, Pages 63-70Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.nbd.2008.12.015
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Funding
- Alzheimer's Disease Research Center [AG025711]
- Byrd Alzheimer's Center and Research Institute
- California Institute for Regenerative Medicine [RN1-00538]
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We have found that a small number of purified Th2-biased A beta-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 A beta. 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 A beta-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 A beta-specific Th2 cells are sufficient to reverse cognitive impairment and provide multiple pathological benefits in an Alzheimer's mouse model. (C) 2008 Elsevier Inc. All rights reserved.
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