Emergence of a broad repertoire of GAD65-specific T-cells in type 1 diabetes patients with graft dysfunction after allogeneic islet transplantation.

フォーマット:

論文

責任表示:

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

言語:

英語

出版情報:

Cognizant Communication Corporation, 2012-09-01

著者名:

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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掲載情報:

Cell Transplantation

ISSN:

0963-6897      

巻:

21

通号:

12

開始ページ:

2783

終了ページ:

2795

バージョン:

publisher

概要:

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. 続きを見る

URL:

http://hdl.handle.net/2297/48419