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We used a bispecific agonist called Immune Modulating Monoclonal-TCR Against Autoimmune Disease (ImmTAAI), consisting of a T cell receptor (TCR) targeting domain fused with a PD-1 agonist to specifically bind beta cells and suppress autoreactive T cells. We used live pancreas slices to demonstrate targeting of ImmTAAI molecules to pre-proinsulin peptide-HLA-A2 complexes on human beta cells. ImmTAAI protected beta cells from T cell killing by increasing T cell motility and inhibiting cytokine secretion. ImmTAAI treatment also increased the motility of islet-infiltrating T cells in slices from a donor with recent-onset T1D and preserved insulin secretion in slices co-cultured with T cell avatars transduced with diabetogenic TCRs. These data demonstrate that ImmTAAI molecules have the potential to limit T cell activity locally, making this an attractive platform to elicit targeted immunoregulation in T1D.<\/jats:p>\n                <jats:sec>\n                  <jats:title>One Sentence Summary<\/jats:title>\n                  <jats:p>We demonstrate inhibition of cellular immunity in human type 1 diabetes using a beta cell-targeting, affinity-enhanced TCR fused to a PD-1 agonist.<\/jats:p>\n                <\/jats:sec>","DOI":"10.1101\/2025.10.21.683528","type":"posted-content","created":{"date-parts":[[2025,10,23]],"date-time":"2025-10-23T02:15:11Z","timestamp":1761185711000},"source":"Crossref","is-referenced-by-count":0,"title":["Inhibition of cell-mediated immunity in type 1 diabetes by beta cell-targeted PD-1 agonists in pancreas tissue slices"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3071-7171","authenticated-orcid":false,"given":"Matthew 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