ArticleThe Journal of clinical investigation2023
Single-cell transcriptomic analysis of renal allograft rejection reveals insights into intragraft TCR clonality.
Article in The Journal of clinical investigation, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
29 citing papers in PubMed, 1 synthesis or guideline pooled it, 45 citations in OpenAlex.
- Immune cell profiling in intestinal transplantation.Human immunology · 2024Pooled it
- Single Cell Multi-Omics Revealing the Important Role of MR1 Mediated MAIT Cells in Maintaining Rejection for Liver Transplantation.Cell proliferation · 2026Article
- Article
- A Comprehensive HLA-DR4 MHC Class II Tetramer Platform for the Detection and Functional Validation of Post-Translational Modification Neoantigens.International journal of molecular sciences · 2026Article
- CD8Molecular therapy : the journal of the American Society of Gene Therapy · 2026Article
- A Subset of Pro-inflammatory CXCL10+ LILRB2+ Macrophages Derives From Recipient Monocytes and Drives Renal Allograft Rejection.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Integrated cross-organ transcriptomic analysis uncovers conserved gene signatures predictive of allograft rejection.PloS one · 2026Article
- Targeted Expansion of Treg Cells to Induce Immune Tolerance after Kidney Transplantation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- T cell-mediated immune responses in xenotransplantation: mechanisms and therapeutic strategies.Frontiers in immunology · 2026Review
- ScRNA profiling of peripheral blood in kidney transplant recipients across rejection responses and treatments.Scientific data · 2025Article
- Single-cell transcriptional landscape of liver transplant rejection reveals tissue persistence of clonally expanded, treatment-resistant T cells.American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons · 2025Article
- CO-STIMULATORY BLOCKADE PREVENTS INTRAGRAFT ACCRUAL OF CLASS-SWITCHED, ACTIVATED B CELLS DESPITE FAILING TO PREVENT T-CELL MEDIATED REJECTION.bioRxiv : the preprint server for biology · 2025Article
- Resolving ScRNA-Seq Signatures of Antigen-Specific CD4bioRxiv : the preprint server for biology · 2025Article
- The Immune Microenvironment of Transplant Glomerulitis.Kidney international reports · 2025Article
- Belatacept and non-melanoma skin cancer risk in kidney transplant recipients: a narrative review from a mechanistic and clinical perspective.BMC nephrology · 2025Review
- Article
- Spatial transcriptomics of Glomerulo-centric antibody mediated rejection in renal transplants.Clinical immunology (Orlando, Fla.) · 2025Article
- FPR1 affects acute rejection in kidney transplantation by regulating iron metabolism in neutrophils.Molecular medicine (Cambridge, Mass.) · 2025Article
- The Evolving T Cell Receptor Recognition Code: The Rules Are More Like Guidelines.Immunological reviews · 2025Review
- The single-cell revolution in transplantation: high-resolution mapping of graft rejection, tolerance, and injury.Frontiers in immunology · 2025Review
Corrections and comments
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Authors and funding
19 authors at 7 institutions in 2 countries.
Funding
Abstract
Bulk analysis of renal allograft biopsies (rBx) identified RNA transcripts associated with acute cellular rejection (ACR); however, these lacked cellular context critical to mechanistic understanding of how rejection occurs despite immunosuppression (IS). We performed combined single-cell RNA transcriptomic and TCR-α/β sequencing on rBx from patients with ACR under differing IS drugs: tacrolimus, iscalimab, and belatacept. We found distinct CD8+ T cell phenotypes (e.g., effector, memory, exhausted) depending upon IS type, particularly within expanded CD8+ T cell clonotypes (CD8EXP). Gene expression of CD8EXP identified therapeutic targets that were influenced by IS type. TCR analysis revealed a highly restricted number of CD8EXP, independent of HLA mismatch or IS type. Subcloning of TCR-α/β cDNAs from CD8EXP into Jurkat 76 cells (TCR-/-) conferred alloreactivity by mixed lymphocyte reaction. Analysis of sequential rBx samples revealed persistence of CD8EXP that decreased, but were not eliminated, after successful antirejection therapy. In contrast, CD8EXP were maintained in treatment-refractory rejection. Finally, most rBx-derived CD8EXP were also observed in matching urine samples, providing precedent for using urine-derived CD8EXP as a surrogate for those found in the rejecting allograft. Overall, our data define the clonal CD8+ T cell response to ACR, paving the next steps for improving detection, assessment, and treatment of rejection.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.