{"created":"2023-06-20T16:34:09.127972+00:00","id":3251,"links":{},"metadata":{"_buckets":{"deposit":"f4dc25ec-73a6-4966-ad9e-59551280b3d0"},"_deposit":{"created_by":3,"id":"3251","owners":[3],"pid":{"revision_id":0,"type":"depid","value":"3251"},"status":"published"},"_oai":{"id":"oai:kindai.repo.nii.ac.jp:00003251","sets":["14:2667:2685:2686","21:2669:2687:2688"]},"author_link":["3602"],"item_8_alternative_title_3":{"attribute_name":"その他（別言語等）のタイトル","attribute_value_mlt":[{"subitem_alternative_title":"Retrovirus evasion of CD8^+ T cell immunity"}]},"item_8_biblio_info_21":{"attribute_name":"書誌情報","attribute_value_mlt":[{"bibliographicIssueDates":{"bibliographicIssueDate":"2011-01-01","bibliographicIssueDateType":"Issued"},"bibliographicPageEnd":"5","bibliographicPageStart":"1","bibliographic_titles":[{"bibliographic_title":"科学研究費補助金研究成果報告書 (2011. )"}]}]},"item_8_description_33":{"attribute_name":"抄録","attribute_value_mlt":[{"subitem_description":"研究成果の概要（和文）：ウイルス等の持続感染個体では、ウイルス特異的メモリーCD8T 細胞に対して特異抗原による継続的な刺激が繰り返されることにより種々の抑制性受容体の発現が持続し、結果T細胞機能が低下するいわゆる疲弊（exhaustion）が起こる。マウスに持続的なウイルス血症とそれに引き続く致死性の赤白血病を誘発するレトロウイルスであるフレンドウイルス（FV）感染個体ではウイルス特異的CD8T 細胞の著しい機能低下が認められるが、その機構は不明であった。研究代表者、はこの機能不全の原因が他の持続感染ウイルス同様の疲弊に起因すること、しかも通常持続感染期にみられるウイルス特異的CD8T 細胞疲弊の誘発が、FV感染個体の場合では感染初期より観察されることを見出した。この成果により、FV 感染により増加した制御性T 細胞（Treg）によりウイルス特異的CD8T 細胞が機能不全に陥るというこれまでの説が根底から覆された。                    研究成果の概要（英文）：During chronic viral infection, persistent exposure to viral antigens leads to the overexpression of multiple inhibitory cell-surface receptors that cause CD8^+ T cell exhaustion. Friend virus (FV) is a murine retrovirus complex that induces acute high-level viremia followed by persistent infection and leukemia development. Here we provide conclusive evidence that FV infection results in the generation of virus-specific effector CD8+ T cells that are terminally exhausted. Acute FV-induced disease is characterized by a rapid increase in the number of virus-infected erythroblasts, leading to massive splenomegaly. Most of the expanded erythroblasts strongly express PD-L1 and MHC class I, thereby creating a highly tolerogenic environment. Consequently, FV-specific effector CD8^+ T cells uniformly express multiple inhibitory receptors, such as PD-1, Tim-3, LAG-3, and CTLA-4, rapidly become non-responsive to restimulation, and are no longer reinvigorated by combined in vivo blockade of PD-1 and Tim-3 during the memory phase. Combined blockade of PD-1 and Tim-3 during the priming/differentiation phase, however, rescued FV-specific CD8+ T cells from becoming terminally exhausted, resulting in improved CD8+ T cell functionality and virus control. These results highlight FV’s unique ability to evade virus-specific CD8^+ T cell responses and the importance of an early prophylactic approach for preventing terminal exhaustion of CD8^+ T cells.","subitem_description_type":"Abstract"}]},"item_8_description_36":{"attribute_name":"内容記述","attribute_value_mlt":[{"subitem_description":"研究種目：若手研究（B）;  研究期間：2010～2011;   課題番号：22790441;   研究分野：医歯薬学;   科研費の分科・細目：基礎医学・ウイルス学","subitem_description_type":"Other"}]},"item_8_description_37":{"attribute_name":"資源タイプ","attribute_value_mlt":[{"subitem_description":"Research Paper","subitem_description_type":"Other"}]},"item_8_description_41":{"attribute_name":"フォーマット","attribute_value_mlt":[{"subitem_description":"application/pdf","subitem_description_type":"Other"}]},"item_8_publisher_14":{"attribute_name":"出版者 名前","attribute_value_mlt":[{"subitem_publisher":"近畿大学"}]},"item_8_relation_11":{"attribute_name":"著者 外部リンク","attribute_value_mlt":[{"subitem_relation_name":[{"subitem_relation_name_text":"http://kaken.nii.ac.jp/d/r/90528564.ja.html"}]}]},"item_8_text_10":{"attribute_name":"著者 役割","attribute_value_mlt":[{"subitem_text_value":"研究代表者"}]},"item_8_text_7":{"attribute_name":"著者(英)","attribute_value_mlt":[{"subitem_text_language":"en","subitem_text_value":"TAKAMURA, SHIKI"}]},"item_8_text_8":{"attribute_name":"著者 所属","attribute_value_mlt":[{"subitem_text_value":"近畿大学医学部; 助教"}]},"item_8_text_9":{"attribute_name":"著者所属(翻訳)","attribute_value_mlt":[{"subitem_text_value":"Kinki University"}]},"item_8_version_type_12":{"attribute_name":"版","attribute_value_mlt":[{"subitem_version_resource":"http://purl.org/coar/version/c_970fb48d4fbd8a85","subitem_version_type":"VoR"}]},"item_creator":{"attribute_name":"著者","attribute_type":"creator","attribute_value_mlt":[{"creatorNames":[{"creatorName":"高村,  史記"},{"creatorName":"タカムラ, シキ","creatorNameLang":"ja-Kana"}],"nameIdentifiers":[{"nameIdentifier":"3602","nameIdentifierScheme":"WEKO"},{"nameIdentifier":"90528564","nameIdentifierScheme":"研究者番号","nameIdentifierURI":" "}]}]},"item_files":{"attribute_name":"ファイル情報","attribute_type":"file","attribute_value_mlt":[{"accessrole":"open_date","date":[{"dateType":"Available","dateValue":"2016-02-17"}],"displaytype":"detail","filename":"KAKEN_22790441seika.pdf","filesize":[{"value":"640.6 kB"}],"format":"application/pdf","licensetype":"license_note","mimetype":"application/pdf","url":{"label":"KAKEN_22790441seika.pdf","url":"https://kindai.repo.nii.ac.jp/record/3251/files/KAKEN_22790441seika.pdf"},"version_id":"b30e12a2-ea52-4d8e-ae6a-834ca4068635"}]},"item_keyword":{"attribute_name":"キーワード","attribute_value_mlt":[{"subitem_subject":"感染防御","subitem_subject_scheme":"Other"},{"subitem_subject":"ワクチン","subitem_subject_scheme":"Other"}]},"item_language":{"attribute_name":"言語","attribute_value_mlt":[{"subitem_language":"jpn"}]},"item_resource_type":{"attribute_name":"資源タイプ","attribute_value_mlt":[{"resourcetype":"research report","resourceuri":"http://purl.org/coar/resource_type/c_18ws"}]},"item_title":"レトロウイルス誘発抗原特異的CD8T細胞機能不全機構の解明","item_titles":{"attribute_name":"タイトル","attribute_value_mlt":[{"subitem_title":"レトロウイルス誘発抗原特異的CD8T細胞機能不全機構の解明"}]},"item_type_id":"8","owner":"3","path":["2686","2688"],"pubdate":{"attribute_name":"公開日","attribute_value":"2012-11-13"},"publish_date":"2012-11-13","publish_status":"0","recid":"3251","relation_version_is_last":true,"title":["レトロウイルス誘発抗原特異的CD8T細胞機能不全機構の解明"],"weko_creator_id":"3","weko_shared_id":-1},"updated":"2023-06-21T01:41:47.768238+00:00"}