Go to JCI Insight
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Publication alerts by email
  • Advertising
  • Job board
  • Contact
  • Clinical Research and Public Health
  • Current issue
  • Past issues
  • By specialty
    • COVID-19
    • Cardiology
    • Gastroenterology
    • Immunology
    • Metabolism
    • Nephrology
    • Neuroscience
    • Oncology
    • Pulmonology
    • Vascular biology
    • All ...
  • Videos
    • Conversations with Giants in Medicine
    • Video Abstracts
  • Reviews
    • View all reviews ...
    • Complement Biology and Therapeutics (May 2025)
    • Evolving insights into MASLD and MASH pathogenesis and treatment (Apr 2025)
    • Microbiome in Health and Disease (Feb 2025)
    • Substance Use Disorders (Oct 2024)
    • Clonal Hematopoiesis (Oct 2024)
    • Sex Differences in Medicine (Sep 2024)
    • Vascular Malformations (Apr 2024)
    • View all review series ...
  • Viewpoint
  • Collections
    • In-Press Preview
    • Clinical Research and Public Health
    • Research Letters
    • Letters to the Editor
    • Editorials
    • Commentaries
    • Editor's notes
    • Reviews
    • Viewpoints
    • 100th anniversary
    • Top read articles

  • Current issue
  • Past issues
  • Specialties
  • Reviews
  • Review series
  • Conversations with Giants in Medicine
  • Video Abstracts
  • In-Press Preview
  • Clinical Research and Public Health
  • Research Letters
  • Letters to the Editor
  • Editorials
  • Commentaries
  • Editor's notes
  • Reviews
  • Viewpoints
  • 100th anniversary
  • Top read articles
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Publication alerts by email
  • Advertising
  • Job board
  • Contact

Citations to this article

Single-cell transcriptomic analysis of renal allograft rejection reveals insights into intragraft TCR clonality
Tiffany Shi, … , E. Steve Woodle, David A. Hildeman
Tiffany Shi, … , E. Steve Woodle, David A. Hildeman
Published May 25, 2023
Citation Information: J Clin Invest. 2023;133(14):e170191. https://doi.org/10.1172/JCI170191.
View: Text | PDF
Research Article Immunology Article has an altmetric score of 580

Single-cell transcriptomic analysis of renal allograft rejection reveals insights into intragraft TCR clonality

  • Text
  • PDF
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.

Authors

Tiffany Shi, Ashley R. Burg, J. Timothy Caldwell, Krishna M. Roskin, Cyd M. Castro-Rojas, P. Chukwunalu Chukwuma, George I. Gray, Sara G. Foote, Jesus A. Alonso, Carla M. Cuda, David A. Allman, James S. Rush, Catherine H. Regnier, Grazyna Wieczorek, Rita R. Alloway, Adele R. Shields, Brian M. Baker, E. Steve Woodle, David A. Hildeman

×

Total citations by year

Year: 2025 2024 2023 Total
Citations: 3 9 2 14
Citation information
This citation data is accumulated from CrossRef, which receives citation information from participating publishers, including this journal. Not all publishers participate in CrossRef, so this information is not comprehensive. Additionally, data may not reflect the most current citations to this article, and the data may differ from citation information available from other sources (for example, Google Scholar, Web of Science, and Scopus).

Citations to this article (14)

Title and authors Publication Year
Pre-Transplant T-Cell Clonal Analysis Identifies CD8+ Donor Reactive Clones that Contribute to Kidney Transplant Rejection
Jes Sanders, Barbara Banbury, Erika Schumacher, Jie He, Yuvaraj Sambandam, Paul A Fields, Lorenzo Gallon, James Mathew, Joseph R Leventhal
Frontiers in immunology 2025
The evolving T cell receptor recognition code: the rules are more like guidelines
Gray GI, Chukwuma PC, Eldaly B, Perera WW, Brambley CA, Rosales TJ, Baker BM
Immunological reviews 2025
FPR1 affects acute rejection in kidney transplantation by regulating iron metabolism in neutrophils
Li P, Ji W, Zhang B, Jia H, Wang J, Sun Z, Wang Y, Wang W, Qi F
Molecular Medicine 2025
Pregnancy programs epigenetic hypofunction in memory CD8+ T cells
Jared Pollard, Grace Hynes, Dengping Yin, Malay Mandal, Fotini Gounari, Maria-Luisa Alegre, Anita Chong
JCI Insight 2024
Defining the T cell transcriptional landscape in pediatric liver transplant rejection at single cell resolution
Peters AL, DePasquale EA, Begum G, Roskin KM, Woodle ES, Hildeman DA
2024
RNA-sequencing of Human Kidney Allografts and Delineation of T-Cell Genes, Gene Sets, and Pathways Associated With Acute T Cell-mediated Rejection.
Mueller FB, Yang H, Li C, Dadhania DM, Xiang JZ, Salvatore SP, Seshan SV, Sharma VK, Suthanthiran M, Muthukumar T
Transplantation 2024
Single-Cell RNA Sequencing in Organ and Cell Transplantation
Abedini-Nassab R, Taheri F, Emamgholizadeh A, Naderi-Manesh H
Biosensors 2024
Immune Cell Profiling in Intestinal Transplantation
Suek N, Young T, Fu J
Human Immunology 2024
Chimerism-Mediated Tolerance in Intestinal Transplantation
Crosby K, Long KD, Fu J
Gastroenterology Clinics of North America 2024
Recognizing Complexity of CD8 T cells in Transplantation
Nicosia M, Valujskikh A
Transplantation 2024
Immunotherapy for Cancer in Kidney Transplant Patients: A Difficult Balance Between Risks and Benefits
Bolufer M, Soler J, Molina M, Taco O, Vila A, Macía M
Transplant International 2024
Cellular Immunity Against BK Polyomavirus in Kidney Transplant Recipients: A Comprehensive Review
Al\u2010Talib M, Skaria A, Griffin S
Transplant Infectious Disease 2024
Multi-omic single cell sequencing: Overview and opportunities for kidney disease therapeutic development
Pregizer S, Vreven T, Mathur M, Robinson LN
Frontiers in Molecular Biosciences 2023
Prior viral infection primes cross-reactive CD8+ T cells that respond to mouse heart allografts
Khorki ME, Shi T, Cianciolo EE, Burg AR, Chukwuma PC, Picarsic JL, Morrice MK, Woodle ES, Maltzman JS, Ferguson A, Katz JD, Baker BM, Hildeman DA
Frontiers in immunology 2023

Advertisement

Copyright © 2025 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

Sign up for email alerts

Picked up by 75 news outlets
Blogged by 2
Posted by 34 X users
Highlighted by 1 platforms
35 readers on Mendeley
See more details