Abeta-specific Th2 cells provide cognitive and pathological benefits to Alzheimer's mice without infiltrating the CNS.
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.
Cao
Chuanhai
C
The Johnnie B. Byrd Sr. Alzheimer's Center and Research Institute, Tampa, FL 33613, USA.
Arendash
Gary W
GW
Dickson
Alexander
A
Mamcarz
Malgorzata B
MB
Lin
Xiaoyang
X
Ethell
Douglas W
DW
D019264:Adoptive Transfer; D000544:Alzheimer Disease / Q000503:physiopathology / Q000628:therapy*; D016229:Amyloid beta-Peptides / Q000097:blood / Q000276:immunology*; D000686:Amyloidosis / Q000628:therapy; D000818:Animals; D003072:Cognition Disorders / Q000503:physiopathology / Q000628:therapy; D004195:Disease Models, Animal; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000097:blood; D006624:Hippocampus / Q000503:physiopathology; D007371:Interferon-gamma / Q000097:blood; D007376:Interleukin-2 / Q000097:blood; D015847:Interleukin-4 / Q000097:blood; D018782:Maze Learning / Q000502:physiology; D008569:Memory Disorders / Q000503:physiopathology / Q000628:therapy; D051379:Mice; D008822:Mice, Transgenic; D017628:Microglia / Q000502:physiology; D018418:Th2 Cells / Q000276:immunology* / Q000637:transplantation; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
D016229:Amyloid beta-Peptides; D007376:Interleukin-2; D014409:Tumor Necrosis Factor-alpha; D015847:Interleukin-4; D007371:Interferon-gamma; D016178:Granulocyte-Macrophage Colony-Stimulating Factor