Integrating TCR gene transduction with FoxP3 genetic engineering enables the reprogramming of human or murine T cells into antigen-specific EngTregs, which then target the defined T1D-relevant peptides (e.g., human G6PC2, GAD65, or PPI, or murine 2.5HIP), endowing them with potent suppressive function. This evidence concerns the gene G6PC2 and type 1 diabetes mellitus.