Elucidation of progressive pathology using PD-1 positive T cells in multiple sclerosis

2019 Fiscal Year Final Research Report

• Project/Area Number: 18K15453
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 52020:Neurology-related
• Research Institution: Kobe University
• Principal Investigator: Chihara Norio 神戸大学, 医学部附属病院, 助教 (70781821)
• Project Period (FY): 2018-04-01 – 2020-03-31
• Keywords: 多発性硬化症 / PD-1 / 共抑制性受容体 / 共抑制性遺伝子プログラム

Outline of Final Research Achievements

Multiple sclerosis (MS) is an autoimmune disease of the central nervous system. In advance to this study, the applicant identified and reported a co-inhibitory gene program (co-iGP) commonly found in multiple T cell dysfunctions such as tumor microenvironment and immune tolerance (Chihara N, et al. Nature 2018). Thus, I hypothesized that this co-iGP in T-cells might control inflammatory pathology and prevent neurological impairments of MS patients who had a good clinical course. Indeed, I found that the proportion of a co-inhibotory receptor PD-1 positivity of cerebrospinal fluid CD8 expressing T cells in MS patients correlated with the therapeutic effects. PD-1+CD8+ T-cells from patients who achieved remission by disease modifying treatments suppressed co-cultured other T-cell proliferations, and their gene expression analysis revealed that other co-inhibitory receptors found in co-iGP were expressed.

Free Research Field

神経免疫学

Academic Significance and Societal Importance of the Research Achievements

本研究で解明を進める遺伝子プログラムはそのT細胞制御機能によって慢性持続炎症制御機序の鍵の一つとして汎用性があり、MS領域のみならず、免疫性神経疾患全般ひいては慢性炎症が二次的増悪因子となる生活習慣病や神経変性疾患など、より広い分野への波及効果が期待できる。今後、他のT細胞機能不全状態との共通性や相違性について解析を加え、免疫性神経疾患全般に応用可能な抑制性遺伝子プログラム同定を目指す。