Analysis of newly identified pathogenic CD4+ helper T-cells in patients with HTLV-1-associated myelopathy

2015 Fiscal Year Final Research Report

• Project/Area Number: 25461294
• 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: Yamano Yoshihisa 聖マリアンナ医科大学, 医学(系)研究科(研究院), 准教授 (80445882)
• Co-Investigator(Kenkyū-buntansha): MISU Tatsuro 東北大学, 医学(系)研究科(研究院), 助教 (00396491)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Keywords: 内科系臨床医学 / 神経内科学 / 神経病態免疫学

Outline of Final Research Achievements

The main feature of Human T-lymphotropic virus type I (HTLV-1) -associated myelopathy (HAM) pathogenesis is a virus-induced hyperactive immune response that produces chronic inflammation in the central nervous system (CNS), but the mechanism by which HTLV-1 deregulates the immune response is unknown. We recently reported a high frequency of HTLV-1-infected CCR4+ cells, including regulatory T cells. We showed that HTLV-1 induces a Th1-like state in these CCR4+ cells via T-bet expression. We have also found that CXCL10 plays an important role in a positive feedback loop that maintains inflammation in the CNS. Astrocytes, which were found to be the main producers of CXCL10 in the CNS, are another key player in the loop. In short, we postulate that infected CCR4+ Th1-like T cells produce interferon-γ, which stimulates astrocytes to produce CXCL10. We now have a much better understanding of the molecular mechanisms at play in HAM pathogenesis.

Free Research Field

神経内科学、神経免疫学、ウイルス免疫学、HTLV-1感染症、HTLV-1関連脊髄症（HAM）