Elucidation of the Expansion Mechanism of Cytotoxic CD4 T Cells During Late-Stage Aging

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K06135
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 43060:System genome science-related
• Research Institution: Osaka University
• Principal Investigator: HASHIMOTO Kosuke 大阪大学, 蛋白質研究所, 准教授 (40624599)
• Co-Investigator(Kenkyū-buntansha): 新井 康通 慶應義塾大学, 看護医療学部(信濃町), 教授 (20255467)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: シングルセル / トランスクリプトーム / スーパーセンチナリアン / CD4キラーT細胞 / 長寿 / 百寿者 / 老化

Outline of Final Research Achievements

In this study, we analyzed cytotoxic CD4 T cells in the peripheral blood of centenarians at the single-cell level and examined their molecular characteristics. First, we investigated the proportion of CD4 killer T cells and found that while the proportion tends to be higher in individuals aged 100 and above, it can also increase in those below this age. Next, we successfully detected a group of T cells with intermediate characteristics between "CD4 helper" and "cytotoxic CD4". These cells exhibited intermediate profiles of surface proteins and cytotoxic genes, suggesting they are transitional cells. Furthermore, we found that many cytotoxic CD4 T cells shared identical TCR sequences, indicating that a very few T cells undergo significant expansion.

Free Research Field

バイオインフォマティクス

Academic Significance and Societal Importance of the Research Achievements

高齢者における感染症の重症化は、免疫機能の低下が主な原因である。特に、獲得免疫の中核を担うT細胞の老化は、免疫防御機能の低下に直結する重大な問題である。本研究は老化後期に特異的に増加するCD4キラーT細胞に注目し、１細胞技術によってT細胞老化の一端を明らかにした。T細胞の老化メカニズムが分子レベルで解明されれば、免疫老化全体に対する理解が進み、健康寿命の延伸に寄与する可能性がある。