Sequencing antagonism between anti-CD3 and antigen-specific tolerance in type 1 diabetes

We build the first mechanistic within-host model of an unexplained pre-clinical drug-drug interaction in type 1 diabetes. Foster et al. (2025, NOD mice) reported that anti-CD3 monoclonal antibody (teplizumab-class) reduces the efficacy of antigen-specific (mRNA/peptide) tolerance immunotherapy - yet both are being pushed toward combination use, making sequencing a live clinical question. A three-state ODE in which autoreactive effectors and antigen-specific Tregs form a bistable switch driving beta-cell mass reproduces the Foster antagonism and yields a falsifiable prediction about how to time and sequence the two therapies. Illustrative modeling hypothesis, not validated clinical findings.