Single-cell RNA sequencing and T cell receptor sequencing of an operational tolerant (OT) pediatric heart transplant recipient and a matched immunosuppressed (IS) control and a healthy control (CTRL).

This dataset investigates the unique immunologic profile of a pediatric heart transplant recipient who achieved operational tolerance (OT), maintaining normal graft function four years after discontinuing all immunosuppressive therapy. Using single-cell RNA sequencing (scRNA-seq) and single-cell T cell receptor sequencing (scTCR-seq), we compared peripheral blood mononuclear cells (PBMCs) and graft-derived cells from this tolerant patient against a matched immunosuppression-dependent control recipient and a healthy control. Our analysis revealed a balanced immune microenvironment in the tolerant patient, characterized by reduced clonal expansion of cytotoxic lymphocytes, controlled CD8+ T cell activation, and altered dendritic cell interactions. Signaling network analysis identified a TGF-β-dominant interaction network, with monocyte-derived dendritic cells (moDCs) showing significant upregulation of TGFBR2. This dataset provides the first comprehensive single-cell map of the immune landscape underlying operational tolerance in pediatric heart transplantation, highlighting a critical role for TGF-β signaling in maintaining graft acceptance. For each subject, cells were processed for single-cell multiplexed RNA sequencing (scRNA-seq) and single-cell T cell receptor sequencing (scTCR-seq) using the 10x Genomics platform. This allowed for simultaneous transcriptome analysis and T-cell clonotype tracking. Processed files for scRNA-seq and TCR annotation files were uploaded.