PD-1 aborts the activation trajectory of autoreactive CD8+ T cells to prohibit their acquisition of effector functions

• Material Type: 博士論文
• ISSN: 0896-8411
• Title: PD-1 aborts the activation trajectory of autoreactive CD8+ T cells to prohibit their acquisition of effector functions
• Author/Editor: Okamura, Hikari; Okazaki, Il-mi; Shimizu, Kenji; Maruhashi, Takumi; Sugiura, Daisuke; Mizuno, Reina; Okazaki, Taku
• Author Heading: Okamura, Hikari; Okazaki, Il-mi; Shimizu, Kenji; Maruhashi, Takumi; Sugiura, Daisuke; Mizuno, Reina; Okazaki, Taku
• Publication, Distribution, etc.: Elsevier Ltd.
• Publication Date: 2019-07-02
• Publication Date (W3CDTF): 2019-07-02
• Alternative Title: PD-1は自己反応性CD８陽性T細胞の活性化経路を遮断して細胞傷害機能の獲得を阻止する
• Periodical title: Journal of Autoimmunity
• Degree grantor/type: 徳島大学
• Date Granted: 2019-07-25
• Date Granted (W3CDTF): 2019-07-25
• Dissertation Number: 甲第3322号
• Degree Type: 博士（医学）
• Conferring No. (Dissertation): 甲第3322号
• Text Language Code: eng
• Subject Heading: 抑制性免疫補助受容体; PD-1; 1型糖尿病; 単一細胞発現解析; 擬似時間解析; Type I diabetes; single cell analysis; pseudotime ordering
• Target Audience: 一般
• Note (General): Anti-PD-1 therapy can induce eradication of tumors and immune-related adverse events (irAEs) in humans and model animals. However, how anti-PD-1 therapy modifies cellular phenotypes of CD8+ T cells to destroy tumors and damage self-tissues remains to be clarified. Here we performed single-cell mRNA expression profiling of autoreactive CD8+ T cells under or beyond PD-1 suppression in target tissues and reconstructed their activation trajectory. Autoreactive CD8+ T cells went through four activation phases and PD-1 strongly attenuated the transition from the second- to the third-phase, where effector functions were acquired. Shifts in cluster composition of autoreactive CD8+ T cells markedly reflected the severity of autoimmunity. In addition, genes up-regulated along the activation-trajectory in autoimmunity were highly expressed in responders of melanoma patients in anti-PD-1 therapy, suggesting that tumor-specific T cells need to be activated in a similar trajectory to destroy tumors in human patients upon PD-1 blockade. These findings reveal that PD-1 blockade facilitates the activation trajectory of CD8+ T cells to boost their effector functions. Targeted manipulation of the trajectory could lead to new therapeutic opportunities.
• DOI: info:doi/10.1016/j.jaut.2019.06.007; https://doi.org/info:doi/10.1016/j.jaut.2019.06.007
• Persistent ID (NDL): info:ndljp/pid/11361582; https://dl.ndl.go.jp/pid/11361582
• Collection: 障害者向け資料
• Collection (Materials For Handicapped People:1): テキストデータ
• Collection (particular): 国立国会図書館デジタルコレクション > デジタル化資料 > 博士論文; https://dl.ndl.go.jp/collections/A00014
• Acquisition Basis: 博士論文（自動収集）
• Date Accepted (W3CDTF): 2019-10-04T14:36:02+09:00
• Format (IMT): application/pdf
• Access Restrictions: 国立国会図書館内限定公開
• Service for the Digitized Contents Transmission Service: 図書館・個人送信対象外
• Availability of remote photoduplication service: 可
• Periodical Title (URI): http://repo.lib.tokushima-u.ac.jp/113693
• Data Provider (Database): 国立国会図書館 : 国立国会図書館デジタルコレクション; https://dl.ndl.go.jp