Evaluating T cell responses prior to the onset of type 1 diabetes

AIMS: In the current study we aimed to evaluat T cell phenotypes and metabolic profiles in high‐risk individuals who progressed to type 1 diabetes compared to those remaining disease free. METHODS: A Fluorspot assay was used to examine T cell responses to a panel of islet autoantigen peptides in samples obtained 6‐ and 30‐months preceding disease onset and at the same timepoints in non‐progressors. RESULTS: We noted a significant increase in the magnitude of the proinflammatory interferon‐γ response to proinsulin and insulin peptides in individuals who progressed to type 1 diabetes. In contrast, in the non‐progressors, we observed an increase in the regulatory IL‐10 response to proinsulin peptides. Furthermore, the T cell responses to the islet peptide panel predisposed towards a proinflammatory interferon‐γ bias in the progressors. CONCLUSIONS: Collectively, these data suggest that a proinflammatory T cell response is prevalent in high‐risk individuals who progress to type 1 diabetes and can be detected up to 6 months prior to onset of disease. This observation, albeit in a small cohort, can potentially be harnessed in disease staging, particularly in identifying autoantibody‐positive individuals transitioning from stage 2 (dysglycemia present and pre‐symptomatic) to stage 3 (dysglycemia present and symptomatic). The detection of these different T cell phenotypes in progressors and non‐progressors suggests the presence of disease endotypes.