Document Detail


Emergence of a Broad Repertoire of GAD65-specific T Cells in Type 1 Diabetes Patients with Graft Dysfunction after Allogeneic Islet Transplantation.
MedLine Citation:
PMID:  22963904     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
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 re-stimulation 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.
Authors:
Daisuke Chujo; Emile Foucat; Morihito Takita; Takeshi Itoh; Koji Sugimoto; Masayuki Shimoda; Kunimasa Yagi; Masakazu Yamagishi; Yoshiko Tamura; Liping Yu; Bashoo Naziruddin; Marlon F Levy; Hideki Ueno; Shinichi Matsumoto
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-9-7
Journal Detail:
Title:  Cell transplantation     Volume:  -     ISSN:  1555-3892     ISO Abbreviation:  Cell Transplant     Publication Date:  2012 Sep 
Date Detail:
Created Date:  2012-9-11     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9208854     Medline TA:  Cell Transplant     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
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