Single-Cell RNA Sequencing of Donor-Reactive T Cells Reveals Role of Apoptosis in Donor-Specific Hyporesponsiveness of Kidney Transplant Recipients

After kidney transplantation (KT), donor-specific hyporesponsiveness (DSH) of recipient T cells develops over time. Recently, apoptosis was identified as a possible underlying mechanism. In this study, both transcriptomic profiles and complete V(D)J variable regions TR transcripts from individual alloreactive transplant recipients were determined with single-cell RNA sequencing. Alloreactive by CD137 expression after stimulation peripheral blood mononuclear obtained KT (N = 7) prior to 3–5 years their donor or third party control. The sorted, sequenced the transcriptome cell receptor analyzed using unsupervised clustering. retain highly polyclonal Cell Receptor Alpha/Beta repertoire Post transplantation, donor-reactive CD4+ had specific downregulation genes involved in cytokine-mediated pathways apoptosis. CD8+ profile did not change significantly Single-cell profiling shows that activated pro-apoptotic clones are preferentially lost stable recipients.