GAD-specific T cells are induced by GAD-alum treatment in Type-1 diabetes patientsShow others and affiliations
2017 (English)In: Clinical Immunology, ISSN 1521-6616, E-ISSN 1521-7035, Vol. 176, p. 114-121Article 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, p. 114-121
Keywords [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, id: 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
2017-04-212017-04-212017-04-21