GAD-specific T cells are induced by GAD-alum treatment in Type-1 diabetes patients

Publication date: Available online 26 January 2017
Source:Clinical Immunology
Author(s): Mikael Pihl, Hugo Barcenilla, Stina Axelsson, Mikael Chéramy, Linda Åkerman, Ingela Johansson, Johnny Ludvigsson, Rosaura Casas
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 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 GAD65 induced 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 CD25^hiCD127^lo. Our findings indicate that GAD-alum treatment primarily induced activated T cells. GAD65-specific cells were mainly of activated phenotype.



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