Neuroprotective effects of CD4+CD25+Foxp3+ regulatory T cells in a 3xTg-AD Alzheimer's disease model

Abstract

// Hyunjung Baek 1 , Minsook Ye 1 , Geun-Hyung Kang 1 , Chanju Lee 1 , Gihyun Lee 1 , Da Bin Choi 1 , Jaehoon Jung 1 , Hyunseong Kim 2 , Seonhwa Lee 3 , Jin Su Kim 3 , Hyun-ju Lee 4 , Insop Shim 4 , Jun-Ho Lee 5 and Hyunsu Bae 1 1 Department of Physiology, College of Korean Medicine, Kyung Hee University, Seoul, Republic of Korea 2 K-herb Research Center, Korea Institute of Oriental Medicine, Yuseongdae-ro, Yuseong-gu, Daejeon, Republic of Korea 3 Division of RI Research, Korea Institute of Radiological & Medical Sciences University of Science & Technology, Gongneug-dong, Nowon-ku, Seoul, Republic of Korea 4 Acupuncture and Meridian Science Research Center, College of Korean Medical Science Graduate School, Kyung Hee University, Seoul, Republic of Korea 5 Department of Biotechnology, Chonnam National University, Gwangju, Republic of Korea Correspondence to: Hyunsu Bae, email: // Keywords : Alzheimer’s disease, regulatory T cells (Treg), amyloid-beta (Aβ) pathology, Immunology and Microbiology Section, Immune response, Immunity Received : July 23, 2016 Accepted : September 29, 2016 Published : October 04, 2016 Abstract 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 six-month-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-D-glucose ([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.