10X single-cell RNA-seq profiling of T cells from the pancreas, pancreatic lymph nodes, and blood of NOD mice with spontaneous or anti-PD-1-induced Type 1 Diabetes

Immune-related adverse events (irAEs) are a notable complication of PD-1 cancer immunotherapy. A better understanding of how these iatrogenic diseases compare to naturally arising autoimmune diseases is needed for treatment and monitoring of irAEs. We identified differences in anti-PD-1-induced Type 1 Diabetes (T1D) and spontaneous T1D in non-obese diabetic (NOD) mice by performing single-cell RNA-seq and TCR-seq on T cells from the pancreas, pancreas-draining lymph node (pLN), and blood of mice with PD-1-induced T1D or spontaneous T1D. In the pancreas, anti-PD-1 resulted in expansion of terminally-exhausted/effector-like CD8+ T cells, an increase in T-bethi CD4+FoxP3- T cells, and a decrease in memory CD4+FoxP3- and CD8+ T cells in contrast to spontaneous T1D. Notably, anti-PD-1 caused increased TCR sharing between the pancreas and the periphery. Moreover, T cells in the blood of anti-PD-1-treated mice expressed markers that differed from spontaneous T1D, suggesting that the blood may provide a window to monitor irAEs rather than relying exclusively on the autoimmune target organ. 10X 5' single cell RNASeq and paired TCR sequencing was performed on sorted TCR-beta+CD11A+ T cells from the pancreas, pancreatic lymph nodes, and peripheral blood of NOD mice. Samples from individual mice were labeled using hashtag antibodies and detected using CITE-seq. Using the TCR sequence as a molecular barcode, we identified matching T cell clones between the pancreatic lymph node, blood and pancreas, and characterized the matching versus non-matching T cell populations within a tissue compartment and between tissue compartments. Please note that processed data files generated from both *FB* and *GEX* raw data are linked to the corresponding *GEX* sample records.