Celiac disease, a gluten-sensitive enteropathy, demonstrates a strong human leukocyte antigen (HLA) association, with more than 90% of patients carrying the HLA-DQ2.5 allotype. No therapy is available for the condition except for a lifelong gluten-free diet. To address this gap, we explored the therapeutic potential of regulatory T cells (T _regs ). By orthotopic replacement of T cell receptors (TCRs) through homology-directed repair, we generated gluten-reactive HLA-DQ2.5-restricted CD4 ⁺ engineered (e) T effector cells (T _effs ) and eT _regs and performed in vivo experiments in HLA-DQ2.5 transgenic mice. Of five validated TCRs, TCRs specific for two immunodominant and deamidated gluten epitopes (DQ2.5-glia-α1a and DQ2.5-glia-α2) were selected for further evaluation. CD4 ⁺ eT _effs exposed to deamidated gluten through oral gavage colocalized with dendritic and B cells in the Peyer's patches and gut-draining lymph nodes and specifically migrated to the intestine. The suppressive function of human eT _regs correlated with high TCR functional activity. eT _regs specific for one epitope suppressed the proliferation and gut migration of CD4 ⁺ eT _effs specific for the same and the other gluten epitope, demonstrating bystander suppression. The suppression requires an antigen-specific activation of eT _regs given that polyclonal T _regs failed to suppress CD4 ⁺ eT _effs . These findings highlight the potential of gluten-reactive eT _regs as a therapeutic for celiac disease.