{"created":"2023-07-27T06:29:40.403700+00:00","id":14443,"links":{},"metadata":{"_buckets":{"deposit":"781e43fb-f09c-49ba-ad90-8325ea87d0f2"},"_deposit":{"created_by":3,"id":"14443","owners":[3],"pid":{"revision_id":0,"type":"depid","value":"14443"},"status":"published"},"_oai":{"id":"oai:kanazawa-u.repo.nii.ac.jp:00014443","sets":["1132:1133:1134"]},"author_link":["25222","25224","25226","438","25227","25223","25228","265","25230","25231","25225","25233","25229","25232"],"item_4_biblio_info_8":{"attribute_name":"書誌情報","attribute_value_mlt":[{"bibliographicIssueDates":{"bibliographicIssueDate":"2012-09-01","bibliographicIssueDateType":"Issued"},"bibliographicIssueNumber":"12","bibliographicPageEnd":"2795","bibliographicPageStart":"2783","bibliographicVolumeNumber":"21","bibliographic_titles":[{"bibliographic_title":"Cell Transplantation"}]}]},"item_4_description_21":{"attribute_name":"抄録","attribute_value_mlt":[{"subitem_description":"Islet transplantation is one of the most promising therapies for type 1 diabetes (T1D). A major issue in islet transplantation is the loss of graft function at late phase. Several studies suggested the involvement of islet-specific T-cells in such islet graft dysfunction. In this study, we investigated the breadth and type of glutamic acid decarboxylase 65 (GAD65)-specific T-cells in T1D patients after allogeneic islet transplantation. Peripheral blood mononuclear cells (PBMCs) were obtained from islet-transplanted T1D patients during insulin-independent period and cultured for 7 days with pools of GAD65 overlapping peptides in the presence of IL-2. Cytokine secretion profiles of peptide-reactive T-cells were analyzed after a short-term restimulation with the same peptides by a multiplex bead-based cytokine assay and by an intracytoplasmic cytokine detection assay. Robust GAD65-specific CD4(+) and CD8(+) T-cell responses were detected in patients who eventually developed chronic graft dysfunction. Multiple GAD65 peptides were found to induce specific T-cell responses in these patients, indicating that the repertoire of GAD65-specific T-cells was broad. Furthermore, GAD65-specific CD4(+) T-cells were composed of heterogeneous populations, which differentially expressed cytokines including IFN-γ and type 2 cytokines, but not IL-10. In contrast, patients who showed only marginal GAD65-specific T-cell responses maintained substantially longer graft survival and insulin independence. In conclusion, our study suggests that the emergence of islet-specific T-cells precedes the development of chronic graft dysfunction in islet-transplanted patients. Thus, our observations support the hypothesis that these islet-specific T-cells contribute to the development of chronic islet graft dysfunction.","subitem_description_type":"Abstract"}]},"item_4_publisher_17":{"attribute_name":"出版者","attribute_value_mlt":[{"subitem_publisher":"Cognizant Communication Corporation"}]},"item_4_relation_12":{"attribute_name":"DOI","attribute_value_mlt":[{"subitem_relation_type":"isIdenticalTo","subitem_relation_type_id":{"subitem_relation_type_id_text":"10.3727/096368912X654993","subitem_relation_type_select":"DOI"}}]},"item_4_source_id_11":{"attribute_name":"NCID","attribute_value_mlt":[{"subitem_source_identifier":"AA1084767X","subitem_source_identifier_type":"NCID"}]},"item_4_source_id_9":{"attribute_name":"ISSN","attribute_value_mlt":[{"subitem_source_identifier":"0963-6897","subitem_source_identifier_type":"ISSN"}]},"item_4_version_type_25":{"attribute_name":"著者版フラグ","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":"Chujo, Daisuke"}],"nameIdentifiers":[{}]},{"creatorNames":[{"creatorName":"Foucat, Emile"}],"nameIdentifiers":[{}]},{"creatorNames":[{"creatorName":"Takita, Morihito"}],"nameIdentifiers":[{}]},{"creatorNames":[{"creatorName":"Itoh, Takeshi"}],"nameIdentifiers":[{}]},{"creatorNames":[{"creatorName":"Sugimoto, Koji"}],"nameIdentifiers":[{}]},{"creatorNames":[{"creatorName":"Shimoda, Masayuki"}],"nameIdentifiers":[{}]},{"creatorNames":[{"creatorName":"Yagi, Kunimasa"}],"nameIdentifiers":[{},{},{},{}]},{"creatorNames":[{"creatorName":"Yamagishi, Masakazu"}],"nameIdentifiers":[{},{},{},{}]},{"creatorNames":[{"creatorName":"Tamura, Yoshiko"}],"nameIdentifiers":[{}]},{"creatorNames":[{"creatorName":"Yu, Liping"}],"nameIdentifiers":[{}]},{"creatorNames":[{"creatorName":"Naziruddin, Bashoo"}],"nameIdentifiers":[{}]},{"creatorNames":[{"creatorName":"Levy, Marlon F."}],"nameIdentifiers":[{}]},{"creatorNames":[{"creatorName":"Ueno, Hideki"}],"nameIdentifiers":[{}]},{"creatorNames":[{"creatorName":"Matsumoto, Shinichi"}],"nameIdentifiers":[{}]}]},"item_files":{"attribute_name":"ファイル情報","attribute_type":"file","attribute_value_mlt":[{"accessrole":"open_date","date":[{"dateType":"Available","dateValue":"2017-10-03"}],"displaytype":"detail","filename":"ME-PR-YAMAGISHI-M-2783.pdf","filesize":[{"value":"747.3 kB"}],"format":"application/pdf","licensetype":"license_note","mimetype":"application/pdf","url":{"label":"ME-PR-YAMAGISHI-M-2783.pdf","url":"https://kanazawa-u.repo.nii.ac.jp/record/14443/files/ME-PR-YAMAGISHI-M-2783.pdf"},"version_id":"0c57e0b0-27f1-4634-8fb2-5b70cce595b8"}]},"item_language":{"attribute_name":"言語","attribute_value_mlt":[{"subitem_language":"eng"}]},"item_resource_type":{"attribute_name":"資源タイプ","attribute_value_mlt":[{"resourcetype":"journal article","resourceuri":"http://purl.org/coar/resource_type/c_6501"}]},"item_title":"Emergence of a broad repertoire of GAD65-specific T-cells in type 1 diabetes patients with graft dysfunction after allogeneic islet transplantation.","item_titles":{"attribute_name":"タイトル","attribute_value_mlt":[{"subitem_title":"Emergence of a broad repertoire of GAD65-specific T-cells in type 1 diabetes patients with graft dysfunction after allogeneic islet transplantation."}]},"item_type_id":"4","owner":"3","path":["1134"],"pubdate":{"attribute_name":"公開日","attribute_value":"2017-10-03"},"publish_date":"2017-10-03","publish_status":"0","recid":"14443","relation_version_is_last":true,"title":["Emergence of a broad repertoire of GAD65-specific T-cells in type 1 diabetes patients with graft dysfunction after allogeneic islet transplantation."],"weko_creator_id":"3","weko_shared_id":-1},"updated":"2023-07-28T00:47:20.866779+00:00"}