1665-P: Uncovering the Cell-Type Specificity in Human T1D Immune Activation Using iPSC-ß-Cells

It is known that T1D involves a complex interaction between pancreatic β-cells and cells of both the innate and adaptive immune systems. Innate immune signaling is involved in the initiation of the autoimmune process, which results in the destruction of β cells by cytotoxic T cells during T1D pathogenesis. Here, we show that exposing human induced pluripotent stem cells derived β cells (hiPSC-β cells) to autologous peripheral immune cells in vitro reveals an activation signature of T1D β cell rejection across multiple immune cell types. We profiled innate and adaptive immune activated populations and identified relevant populations to T1D autoimmunity. After co-culture of donor-matched target and effector cells, we performed mass cytometry (CyTOF). We used an immunophenotyping CyTOF panel containing 32 markers to identify activation in different immune populations. As a negative control, we used unstimulated effector peripheral immune cells. As a positive control, we used unmatched β cells from other donors. Finally, all experiments were performed with hiPSC-α cells and donor-matched peripheral immune cells, and we did not observe the activation of immune cells in the hiPSC-α cells donor-matched coculture. Exposing T1D hiPSC-β cells to donor-matched peripheral immune cells in vitro revealed the activation of distinct immune cell populations that participate in T1D β cell rejection. We observed differences within T1D patient samples, we anticipate that we can use this model to study T1D patient heterogeneity.