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Emergence of a broad repertoire of GAD65-specific T-cells in type 1 diabetes patients with graft dysfunction after allogeneic islet transplantation.
http://hdl.handle.net/2297/48419
http://hdl.handle.net/2297/48419ed17b738-831e-411f-9992-8014e63fae0f
| 名前 / ファイル | ライセンス | アクション |
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ME-PR-YAMAGISHI-M-2783.pdf (747.3 kB)
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| Item type | 学術雑誌論文 / Journal Article(1) | |||||
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| 公開日 | 2017-10-03 | |||||
| タイトル | ||||||
| タイトル | Emergence of a broad repertoire of GAD65-specific T-cells in type 1 diabetes patients with graft dysfunction after allogeneic islet transplantation. | |||||
| 言語 | ||||||
| 言語 | eng | |||||
| 資源タイプ | ||||||
| 資源タイプ識別子 | http://purl.org/coar/resource_type/c_6501 | |||||
| 資源タイプ | journal article | |||||
| 著者 |
Chujo, Daisuke
× Chujo, Daisuke× Foucat, Emile× Takita, Morihito× Itoh, Takeshi× Sugimoto, Koji× Shimoda, Masayuki× Yagi, Kunimasa× Yamagishi, Masakazu× Tamura, Yoshiko× Yu, Liping× Naziruddin, Bashoo× Levy, Marlon F.× Ueno, Hideki× Matsumoto, Shinichi |
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| 書誌情報 |
Cell Transplantation 巻 21, 号 12, p. 2783-2795, 発行日 2012-09-01 |
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| ISSN | ||||||
| 収録物識別子タイプ | ISSN | |||||
| 収録物識別子 | 0963-6897 | |||||
| NCID | ||||||
| 収録物識別子タイプ | NCID | |||||
| 収録物識別子 | AA1084767X | |||||
| DOI | ||||||
| 関連タイプ | isIdenticalTo | |||||
| 識別子タイプ | DOI | |||||
| 関連識別子 | 10.3727/096368912X654993 | |||||
| 出版者 | ||||||
| 出版者 | Cognizant Communication Corporation | |||||
| 抄録 | ||||||
| 内容記述タイプ | Abstract | |||||
| 内容記述 | 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. | |||||
| 著者版フラグ | ||||||
| 出版タイプ | VoR | |||||
| 出版タイプResource | http://purl.org/coar/version/c_970fb48d4fbd8a85 | |||||
