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

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.