Type 1 diabetes (T1D) is an autoimmune disease caused by the loss of self-tolerance toward insulin-producing pancreatic β-cells. Its etiology remains incompletely understood but involves dysregulated T cell responses. Here, we perform single-cell transcriptomic analysis of peripheral blood T cells from children newly diagnosed with T1D, the same children after one year, and healthy donors. We observe that children with diabetes show diminished effector and cytotoxic programs and enhanced stemness-associated gene signature across diverse T cell subsets, especially at diagnosis. In parallel, we detect signs of impaired regulatory capacity in regulatory T cells and regulatory TR3-56 cells. These findings are supported by flow cytometry analysis of the same cohort and reanalysis of publicly available datasets. Overall, our results suggest that T1D is associated with impaired T cell effector differentiation and regulatory T cell dysfunction, both of which may contribute to immune imbalance and loss of self-tolerance.

Department of Bioinformatics 2nd Faculty of Medicine Charles University Prague Czechia

Department of Cell Biology Faculty of Science Charles University Prague Czechia

Department of Pediatrics 2nd Faculty of Medicine Charles University and Motol University Hospital Prague Czechia

Laboratory of Adaptive Immunity Institute of Molecular Genetics of the Czech Academy of Sciences Prague Czechia

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