Development of abnormal immune system by regulatory T-cell specific HTLV-1 expression in HAM/TSP

2015 Fiscal Year Final Research Report

• Project/Area Number: 24790898
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Neurology
• Research Institution: St. Marianna University School of Medicine
• Principal Investigator: Araya Natsumi 聖マリアンナ医科大学, 医学(系)研究科(研究院), 助教 (80440353)
• Project Period (FY): 2012-04-01 – 2016-03-31
• Keywords: HTLV-1 / HTLV-1関連脊髄症 / Tax / 制御性T細胞 / IFN-γ

Outline of Final Research Achievements

Human T-lymphotropic virus type 1 (HTLV-1) harness CD4+ T-cell plasticity to effect changes in infected T-cells via HTLV-1 Tax that cause once suppressive Treg cells to lose FOXP3 expression and produce IFN-γ. We hypothesized that the transformation of Tax expressed Treg cells plays a key role in the pathogenesis of HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP).
In this study, I created the knock-in mice expressing Tax in treg cells and indicated some abnormal immune responses in this mouse (chronic inflammation of the ear and tail, inflammatory cytokine production from spleen cells and hyper-responsiveness to EAE). Therefore, these results suggested that abnormal immune responses induced by expression of Tax in Treg cells play an important role in development and pathogenesis of HAM/TSP.

Free Research Field

医歯薬学