Single-cell RNA sequencing reveals peripheral blood mononuclear immune cell landscape associated with operational tolerance in a kidney transplant recipient.

Operational tolerance (OT) after kidney transplantation is defined as stable graft acceptance without the need for immunosuppression therapy. However, it is not clear which cellular and molecular pathways are driving tolerance in these patients. In this first-of-its-kind pilot study, we assessed the immune landscape associated with OT using single-cell (sc) analyses. Peripheral mononuclear cells (PBMCs) from a kidney transplant recipient (KTR) with OT (Tol), two healthy individuals (HC), and a KTR with normal kidney function on standard-of-care immunosuppression (SOC) evaluated. The immune landscape of the Tol was drastically different from SOC and emerges closer to the profile of HC. TCL1A naïve B-cells and LSGAL1 regulatory T cells (Tregs) were in higher proportions in Tol. We were unable to identify Treg sub-cluster in SOC. The ligand-receptor (LR) analysis in HC and Tol identified interactions between B-cells and Tregs that enhance the proliferation and suppressive function of Tregs. SOC reported highest proportion of activated B-cells with more cells in G2M phase. Our sc-RNAseq study identified the mediators of tolerance however it emphasizes the requirement of similar investigation on a larger cohort to re-affirm the role of immune cells in tolerance.