Single-cell transcriptomics reveal that PD-1 mediates immune tolerance by regulating proliferation of regulatory T-cells. Mus musculus

We demonstrate that coreceptor and costimulation blockade also promoted transplant tolerance to hESC-derived pancreatic islets in non-obese diabetic (NOD) mice via Treg. By single-cell RNA-sequencing (scRNA-seq), we performed genome-wide characterization of 12,964 intragraft CD4+ T-cells including conventional T-cells and Treg of both rejecting and tolerized grafts. We show that conventional T-cells found in the tolerized grafts expressed genes that have been reported to support Treg function. Moreover, Treg were heterogeneous in determining transplant outcome; and there were at least two subsets of Treg in rejecting grafts that were less proliferative and distinct from those in tolerized grafts.