Developmental mechanism of regulatory T cell-derived abnormal T cells identified by HAM

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K09702
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Neurology
• Research Institution: St. Marianna University School of Medicine
• Principal Investigator: Sato Tomoo 聖マリアンナ医科大学, 医学研究科, 准教授 (30387063)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: HTLV-1 / Tax / 制御性T細胞 / HTLV-1関連脊髄症

Outline of Final Research Achievements

Transdifferentiation of regulatory T cells (Treg) into Th1-like cells by HTLV-1 Tax is important for the pathogenesis of HTLV-1-associated myelopathy (HAM). However, the in vivo pathogenicity has not been clarified. Therefore, unlike previous Tax-expressing mice, we generated mice in which Tax expression was restricted to Treg and only one copy of Tax was expressed per cell. When expressed Tax homotypically, 28 of 28 mice (100%) died by 6 week-old, and all mice which expressed Tax heterogeneously had dermatitis and ulcers on the tail and pinna by 20 week-old. Thus, the in vivo pathogenicity of Treg-specific Tax expression was revealed.

Free Research Field

神経免疫学

Academic Significance and Societal Importance of the Research Achievements

本研究により、HTLV-1 Taxが発現する感染細胞の病原性が個体レベルにおいても重要であることが判明した。また、われわれが実施したHAM患者を対象とした抗CCR4抗体の早期臨床試験より、HTLV-1感染細胞を破壊することが、脊髄の炎症レベルを改善するだけでなく、臨床症状まで改善させる可能性が高く、これらを考え合わせると、HTLV-1感染細胞がHAMの病態に継続的に関与していることが明確となった。