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GAD-specific T cells are induced by GAD-alum treatment in Type-1 diabetes patients
Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.
Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.
Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.
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2017 (English)In: Clinical Immunology, ISSN 1521-6616, E-ISSN 1521-7035, Vol. 176, 114-121 p.Article in journal (Refereed) Published
Abstract [en]

Administration of Glutamic Acid Decarboxylase (GAD)(65) formulated in aluminium hydroxide preserved insulin secretion in a phase II trial in recent onset Type 1 Diabetes. A subsequent European phase III trial was closed at 15 months after failing to reach primary endpoint, but the majority of the Swedish patients completed the 21 months follow-up. We studied the frequencies and phenotype of T cells, suppressive capacity of Tregs, GAD(65)-induced proliferation, and frequencies of T cells with a GAD(65)-specific TCR in Swedes participating in the trial. Stimulation with GAD(65) induced activated T cells and also cells with a suppressive phenotype. Activated GAD(65)-specific effector T cells were detected by tetramer staining while the frequency of GAD(65)-specific Treg was not affected by the treatment. Additional doses of GAD-alum increased frequencies of CD25(+)CD127(+), but had no effect on CD25(hi)CD127(lo). Our findings indicate that GAD-alum treatment primarily induced activated T cells. GAD(65)-specific cells were mainly of activated phenotype. (C) 2017 Elsevier Inc. All rights reserved.

Place, publisher, year, edition, pages
ACADEMIC PRESS INC ELSEVIER SCIENCE , 2017. Vol. 176, 114-121 p.
Keyword [en]
Type 1 diabetes; Regulatory T cells; Immune intervention; GAD; Children
National Category
Immunology
Identifiers
URN: urn:nbn:se:liu:diva-136608DOI: 10.1016/j.clim.2017.01.010ISI: 000396965200015PubMedID: 28131926OAI: oai:DiVA.org:liu-136608DiVA: diva2:1089936
Note

Funding Agencies|Juvenile Diabetes Research Foundation [17-2011-249]; Swedish Child Diabetes Foundation (Barndiabetesfonden); Medical Research Council of Southeast Sweden [161081]; Diamyd Medical

Available from: 2017-04-21 Created: 2017-04-21 Last updated: 2017-04-21

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Pihl, MikaelBarcenilla, HugoAxelsson Chéramy, StinaChéramy, MikaelÅkerman, LindaJohansson, IngelaLudvigsson, JohnnyCasas, Rosaura
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Division of Microbiology and Molecular MedicineFaculty of Medicine and Health SciencesDivision of Clinical SciencesDivision of Children's and Women's healthDepartment of Paediatrics in Linköping
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