02414nas a2200325   4500000000100000000000100001008004100002260001500043653001900058653001800077653003100095653002000126653004500146100003200191700002400223700001400247700001900261700001600280700002000296700002600316700002100342700002400363700002000387700001600407700002300423245010900446300001100555520150800566022001402074       2025                            d  c2025-09-2610aCD8⁺ T cells10aHLA‐B*57:0110aimmune‐mediated toxicity10aliver organoids10aorganoid‐immune co‐culture platforms1 aFadoua El Abdellaoui Soussi1 aMichael Brusilovsky1 aEmma Buck1 aW. Clark Bacon1 aSina Dadgar1 aAaron Fullerton1 aVictoria Marsh Durban1 aRiccardo Barrile1 aMichael A. Helmrath1 aTakanori Takebe1 aAdrian Roth1 aMagdalena Kasendra00aAutologous Organoid-T Cell Co-Culture Platform for Modeling of Immune-Mediated Drug-Induced Liver Injury  ae085843 aModeling adaptive immune responses in induced pluripotent stem cell (iPSC)-derived liver systems remains a critical barrier for studying immune-mediated hepatic diseases, including idiosyncratic drug-induced liver injury (iDILI). Conventional hepatotoxicity models lack the components required to capture patient-specific, T cell-mediated injury. Here, a scalable and matrix-free human liver organoid (HLO) microarray platform is presented that enables controlled co-culture of Human Leukocyte Antigen (HLA)-genotyped, iPSC-derived HLOs with autologous CD8⁺ T cells. This immune-competent system supports antigen-specific T cell activation and reproduces cytotoxic effector responses in a genetically defined context. As a proof-of-concept, the platform models clinically relevant iDILI caused by flucloxacillin in HLA-B*57:01 carriers, recapitulating CD8⁺ T cell proliferation, hepatocyte apoptosis, and variability in immune responses across donors. The system captures hallmark features of adaptive immune-mediated hepatotoxicity, including secretion of tumor necrosis factor-alpha and Granzyme B, and cytokeratin-18 release from injured hepatocytes. By linking genetic susceptibility with functional immune outcomes, this platform provides a modular and scalable approach for evaluating immune-mediated toxicities. The method offers broad utility for mechanistic studies of drug hypersensitivity, immune-related adverse events, and preclinical safety assessment in support of precision medicine.  a2198-3844