title: GAD-specific T cells are induced by GAD-alum treatment in Type-1 diabetes patients.
abstract: Administration of Glutamic Acid Decarboxylase (GAD)65formulated 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 15months after failing to reach primary endpoint, but the majority of the Swedish patients completed the 21months follow-up. We studied the frequencies and phenotype of T cells, suppressive capacity of Tregs, GAD65-induced proliferation, and frequencies of T cells with a GAD65-specific TCR in Swedes participating in the trial. Stimulation with GAD65induced activated T cells and also cells with a suppressive phenotype. Activated GAD65-specific effector T cells were detected by tetramer staining while the frequency of GAD65-specific Treg was not affected by the treatment. Additional doses of GAD-alum increased frequencies of CD25+CD127+, but had no effect on CD25hiCD127lo. Our findings indicate that GAD-alum treatment primarily induced activated T cells. GAD65-specific cells were mainly of activated phenotype.
authors.affiliation: Division of Clinical Sciences, Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
authors.forename: Mikael
authors.initials: M
authors.lastname: Pihl
authors.affiliation: Division of Clinical Sciences, Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden. Electronic address: hugo.barcenilla@liu.se.
authors.forename: Hugo
authors.initials: H
authors.lastname: Barcenilla
authors.affiliation: Division of Clinical Sciences, Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
authors.forename: Stina
authors.initials: S
authors.lastname: Axelsson
authors.affiliation: Division of Clinical Sciences, Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
authors.forename: Mikael
authors.initials: M
authors.lastname: Chéramy
authors.affiliation: Division of Clinical Sciences, Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
authors.forename: Linda
authors.initials: L
authors.lastname: Åkerman
authors.affiliation: Division of Clinical Sciences, Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
authors.forename: Ingela
authors.initials: I
authors.lastname: Johansson
authors.affiliation: Division of Clinical Sciences, Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
authors.forename: Johnny
authors.initials: J
authors.lastname: Ludvigsson
authors.affiliation: Division of Clinical Sciences, Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
authors.forename: Rosaura
authors.initials: R
authors.lastname: Casas
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy* / Q000276:immunology*; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D005968:Glutamate Decarboxylase / Q000008:administration & dosage*; D006801:Humans; D053645:Interleukin-2 Receptor alpha Subunit / Q000276:immunology; D053699:Interleukin-7 Receptor alpha Subunit / Q000276:immunology; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D008297:Male; D013548:Sweden; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects* / Q000276:immunology*; D055815:Young Adult
chemical_list: D053645:Interleukin-2 Receptor alpha Subunit; D053699:Interleukin-7 Receptor alpha Subunit; D005968:Glutamate Decarboxylase
keywords: Children; GAD; Immune intervention; Regulatory T cells; Type 1 diabetes