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ResearchIn-Press PreviewImmunologyTransplantation Open Access | 10.1172/JCI170191

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

Tiffany Shi,1 Ashley R. Burg,1 J. Timothy Caldwell,2 Krishna M. Roskin,3 Cyd M. Castro-Rojas,1 P. Chukwunalu Chukwuma,4 George I. Gray,4 Sara G. Foote,4 Jesus A. Alonso,4 Carla M. Cuda,5 David A. Allman,6 James S. Rush,7 Catherine H. Regnier,7 Grazyna Wieczorek,7 Rita R. Alloway,8 Adele R. Shields,9 Brian M. Baker,4 E. Steve Woodle,9 and David A. Hildeman1

1Division of Immunobiology, Cincinnati Children's Hospital Medical Center, Cincinnati, United States of America

2Division of Nephrology and Hypertension, Cincinnati Children's Hospital Medical Center, Cincinnati, United States of America

3Division of Biomedical Informatics, Cincinnati Children's Hospital Medical Center, Cincinnati, United States of America

4Department of Chemistry and Biochemistry and the Harper Cancer Research Ins, University of Notre Dame, South Bend, United States of America

5Division of Rheumatology, Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, United States of America

6Department of Pathology and Laboratory Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, United States of America

7Immunology Disease Area, Novartis Institutes for BioMedical Research, Basel, Switzerland

8Division of Nephrology and Hypertension, Department of Internal Medicine, University of Cincinnati College of Medicine, Cincinnati, United States of America

9Division of Transplantation, Department of Surgery, University of Cincinnati College of Medicine, Cincinnati, United States of America

10Department of Chemistry and Biochemistry and the Harper Cancer Research Ins, University of Notre Dame, Notre Dame, United States of America

Find articles by Shi, T. in: JCI | PubMed | Google Scholar |

1Division of Immunobiology, Cincinnati Children's Hospital Medical Center, Cincinnati, United States of America

2Division of Nephrology and Hypertension, Cincinnati Children's Hospital Medical Center, Cincinnati, United States of America

3Division of Biomedical Informatics, Cincinnati Children's Hospital Medical Center, Cincinnati, United States of America

4Department of Chemistry and Biochemistry and the Harper Cancer Research Ins, University of Notre Dame, South Bend, United States of America

5Division of Rheumatology, Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, United States of America

6Department of Pathology and Laboratory Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, United States of America

7Immunology Disease Area, Novartis Institutes for BioMedical Research, Basel, Switzerland

8Division of Nephrology and Hypertension, Department of Internal Medicine, University of Cincinnati College of Medicine, Cincinnati, United States of America

9Division of Transplantation, Department of Surgery, University of Cincinnati College of Medicine, Cincinnati, United States of America

10Department of Chemistry and Biochemistry and the Harper Cancer Research Ins, University of Notre Dame, Notre Dame, United States of America

Find articles by Burg, A. in: JCI | PubMed | Google Scholar |

1Division of Immunobiology, Cincinnati Children's Hospital Medical Center, Cincinnati, United States of America

2Division of Nephrology and Hypertension, Cincinnati Children's Hospital Medical Center, Cincinnati, United States of America

3Division of Biomedical Informatics, Cincinnati Children's Hospital Medical Center, Cincinnati, United States of America

4Department of Chemistry and Biochemistry and the Harper Cancer Research Ins, University of Notre Dame, South Bend, United States of America

5Division of Rheumatology, Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, United States of America

6Department of Pathology and Laboratory Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, United States of America

7Immunology Disease Area, Novartis Institutes for BioMedical Research, Basel, Switzerland

8Division of Nephrology and Hypertension, Department of Internal Medicine, University of Cincinnati College of Medicine, Cincinnati, United States of America

9Division of Transplantation, Department of Surgery, University of Cincinnati College of Medicine, Cincinnati, United States of America

10Department of Chemistry and Biochemistry and the Harper Cancer Research Ins, University of Notre Dame, Notre Dame, United States of America

Find articles by Caldwell, J. in: JCI | PubMed | Google Scholar |

1Division of Immunobiology, Cincinnati Children's Hospital Medical Center, Cincinnati, United States of America

2Division of Nephrology and Hypertension, Cincinnati Children's Hospital Medical Center, Cincinnati, United States of America

3Division of Biomedical Informatics, Cincinnati Children's Hospital Medical Center, Cincinnati, United States of America

4Department of Chemistry and Biochemistry and the Harper Cancer Research Ins, University of Notre Dame, South Bend, United States of America

5Division of Rheumatology, Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, United States of America

6Department of Pathology and Laboratory Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, United States of America

7Immunology Disease Area, Novartis Institutes for BioMedical Research, Basel, Switzerland

8Division of Nephrology and Hypertension, Department of Internal Medicine, University of Cincinnati College of Medicine, Cincinnati, United States of America

9Division of Transplantation, Department of Surgery, University of Cincinnati College of Medicine, Cincinnati, United States of America

10Department of Chemistry and Biochemistry and the Harper Cancer Research Ins, University of Notre Dame, Notre Dame, United States of America

Find articles by Roskin, K. in: JCI | PubMed | Google Scholar |

1Division of Immunobiology, Cincinnati Children's Hospital Medical Center, Cincinnati, United States of America

2Division of Nephrology and Hypertension, Cincinnati Children's Hospital Medical Center, Cincinnati, United States of America

3Division of Biomedical Informatics, Cincinnati Children's Hospital Medical Center, Cincinnati, United States of America

4Department of Chemistry and Biochemistry and the Harper Cancer Research Ins, University of Notre Dame, South Bend, United States of America

5Division of Rheumatology, Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, United States of America

6Department of Pathology and Laboratory Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, United States of America

7Immunology Disease Area, Novartis Institutes for BioMedical Research, Basel, Switzerland

8Division of Nephrology and Hypertension, Department of Internal Medicine, University of Cincinnati College of Medicine, Cincinnati, United States of America

9Division of Transplantation, Department of Surgery, University of Cincinnati College of Medicine, Cincinnati, United States of America

10Department of Chemistry and Biochemistry and the Harper Cancer Research Ins, University of Notre Dame, Notre Dame, United States of America

Find articles by Castro-Rojas, C. in: JCI | PubMed | Google Scholar |

1Division of Immunobiology, Cincinnati Children's Hospital Medical Center, Cincinnati, United States of America

2Division of Nephrology and Hypertension, Cincinnati Children's Hospital Medical Center, Cincinnati, United States of America

3Division of Biomedical Informatics, Cincinnati Children's Hospital Medical Center, Cincinnati, United States of America

4Department of Chemistry and Biochemistry and the Harper Cancer Research Ins, University of Notre Dame, South Bend, United States of America

5Division of Rheumatology, Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, United States of America

6Department of Pathology and Laboratory Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, United States of America

7Immunology Disease Area, Novartis Institutes for BioMedical Research, Basel, Switzerland

8Division of Nephrology and Hypertension, Department of Internal Medicine, University of Cincinnati College of Medicine, Cincinnati, United States of America

9Division of Transplantation, Department of Surgery, University of Cincinnati College of Medicine, Cincinnati, United States of America

10Department of Chemistry and Biochemistry and the Harper Cancer Research Ins, University of Notre Dame, Notre Dame, United States of America

Find articles by Chukwuma, P. in: JCI | PubMed | Google Scholar

1Division of Immunobiology, Cincinnati Children's Hospital Medical Center, Cincinnati, United States of America

2Division of Nephrology and Hypertension, Cincinnati Children's Hospital Medical Center, Cincinnati, United States of America

3Division of Biomedical Informatics, Cincinnati Children's Hospital Medical Center, Cincinnati, United States of America

4Department of Chemistry and Biochemistry and the Harper Cancer Research Ins, University of Notre Dame, South Bend, United States of America

5Division of Rheumatology, Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, United States of America

6Department of Pathology and Laboratory Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, United States of America

7Immunology Disease Area, Novartis Institutes for BioMedical Research, Basel, Switzerland

8Division of Nephrology and Hypertension, Department of Internal Medicine, University of Cincinnati College of Medicine, Cincinnati, United States of America

9Division of Transplantation, Department of Surgery, University of Cincinnati College of Medicine, Cincinnati, United States of America

10Department of Chemistry and Biochemistry and the Harper Cancer Research Ins, University of Notre Dame, Notre Dame, United States of America

Find articles by Gray, G. in: JCI | PubMed | Google Scholar

1Division of Immunobiology, Cincinnati Children's Hospital Medical Center, Cincinnati, United States of America

2Division of Nephrology and Hypertension, Cincinnati Children's Hospital Medical Center, Cincinnati, United States of America

3Division of Biomedical Informatics, Cincinnati Children's Hospital Medical Center, Cincinnati, United States of America

4Department of Chemistry and Biochemistry and the Harper Cancer Research Ins, University of Notre Dame, South Bend, United States of America

5Division of Rheumatology, Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, United States of America

6Department of Pathology and Laboratory Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, United States of America

7Immunology Disease Area, Novartis Institutes for BioMedical Research, Basel, Switzerland

8Division of Nephrology and Hypertension, Department of Internal Medicine, University of Cincinnati College of Medicine, Cincinnati, United States of America

9Division of Transplantation, Department of Surgery, University of Cincinnati College of Medicine, Cincinnati, United States of America

10Department of Chemistry and Biochemistry and the Harper Cancer Research Ins, University of Notre Dame, Notre Dame, United States of America

Find articles by Foote, S. in: JCI | PubMed | Google Scholar

1Division of Immunobiology, Cincinnati Children's Hospital Medical Center, Cincinnati, United States of America

2Division of Nephrology and Hypertension, Cincinnati Children's Hospital Medical Center, Cincinnati, United States of America

3Division of Biomedical Informatics, Cincinnati Children's Hospital Medical Center, Cincinnati, United States of America

4Department of Chemistry and Biochemistry and the Harper Cancer Research Ins, University of Notre Dame, South Bend, United States of America

5Division of Rheumatology, Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, United States of America

6Department of Pathology and Laboratory Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, United States of America

7Immunology Disease Area, Novartis Institutes for BioMedical Research, Basel, Switzerland

8Division of Nephrology and Hypertension, Department of Internal Medicine, University of Cincinnati College of Medicine, Cincinnati, United States of America

9Division of Transplantation, Department of Surgery, University of Cincinnati College of Medicine, Cincinnati, United States of America

10Department of Chemistry and Biochemistry and the Harper Cancer Research Ins, University of Notre Dame, Notre Dame, United States of America

Find articles by Alonso, J. in: JCI | PubMed | Google Scholar

1Division of Immunobiology, Cincinnati Children's Hospital Medical Center, Cincinnati, United States of America

2Division of Nephrology and Hypertension, Cincinnati Children's Hospital Medical Center, Cincinnati, United States of America

3Division of Biomedical Informatics, Cincinnati Children's Hospital Medical Center, Cincinnati, United States of America

4Department of Chemistry and Biochemistry and the Harper Cancer Research Ins, University of Notre Dame, South Bend, United States of America

5Division of Rheumatology, Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, United States of America

6Department of Pathology and Laboratory Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, United States of America

7Immunology Disease Area, Novartis Institutes for BioMedical Research, Basel, Switzerland

8Division of Nephrology and Hypertension, Department of Internal Medicine, University of Cincinnati College of Medicine, Cincinnati, United States of America

9Division of Transplantation, Department of Surgery, University of Cincinnati College of Medicine, Cincinnati, United States of America

10Department of Chemistry and Biochemistry and the Harper Cancer Research Ins, University of Notre Dame, Notre Dame, United States of America

Find articles by Cuda, C. in: JCI | PubMed | Google Scholar |

1Division of Immunobiology, Cincinnati Children's Hospital Medical Center, Cincinnati, United States of America

2Division of Nephrology and Hypertension, Cincinnati Children's Hospital Medical Center, Cincinnati, United States of America

3Division of Biomedical Informatics, Cincinnati Children's Hospital Medical Center, Cincinnati, United States of America

4Department of Chemistry and Biochemistry and the Harper Cancer Research Ins, University of Notre Dame, South Bend, United States of America

5Division of Rheumatology, Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, United States of America

6Department of Pathology and Laboratory Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, United States of America

7Immunology Disease Area, Novartis Institutes for BioMedical Research, Basel, Switzerland

8Division of Nephrology and Hypertension, Department of Internal Medicine, University of Cincinnati College of Medicine, Cincinnati, United States of America

9Division of Transplantation, Department of Surgery, University of Cincinnati College of Medicine, Cincinnati, United States of America

10Department of Chemistry and Biochemistry and the Harper Cancer Research Ins, University of Notre Dame, Notre Dame, United States of America

Find articles by Allman, D. in: JCI | PubMed | Google Scholar |

1Division of Immunobiology, Cincinnati Children's Hospital Medical Center, Cincinnati, United States of America

2Division of Nephrology and Hypertension, Cincinnati Children's Hospital Medical Center, Cincinnati, United States of America

3Division of Biomedical Informatics, Cincinnati Children's Hospital Medical Center, Cincinnati, United States of America

4Department of Chemistry and Biochemistry and the Harper Cancer Research Ins, University of Notre Dame, South Bend, United States of America

5Division of Rheumatology, Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, United States of America

6Department of Pathology and Laboratory Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, United States of America

7Immunology Disease Area, Novartis Institutes for BioMedical Research, Basel, Switzerland

8Division of Nephrology and Hypertension, Department of Internal Medicine, University of Cincinnati College of Medicine, Cincinnati, United States of America

9Division of Transplantation, Department of Surgery, University of Cincinnati College of Medicine, Cincinnati, United States of America

10Department of Chemistry and Biochemistry and the Harper Cancer Research Ins, University of Notre Dame, Notre Dame, United States of America

Find articles by Rush, J. in: JCI | PubMed | Google Scholar

1Division of Immunobiology, Cincinnati Children's Hospital Medical Center, Cincinnati, United States of America

2Division of Nephrology and Hypertension, Cincinnati Children's Hospital Medical Center, Cincinnati, United States of America

3Division of Biomedical Informatics, Cincinnati Children's Hospital Medical Center, Cincinnati, United States of America

4Department of Chemistry and Biochemistry and the Harper Cancer Research Ins, University of Notre Dame, South Bend, United States of America

5Division of Rheumatology, Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, United States of America

6Department of Pathology and Laboratory Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, United States of America

7Immunology Disease Area, Novartis Institutes for BioMedical Research, Basel, Switzerland

8Division of Nephrology and Hypertension, Department of Internal Medicine, University of Cincinnati College of Medicine, Cincinnati, United States of America

9Division of Transplantation, Department of Surgery, University of Cincinnati College of Medicine, Cincinnati, United States of America

10Department of Chemistry and Biochemistry and the Harper Cancer Research Ins, University of Notre Dame, Notre Dame, United States of America

Find articles by Regnier, C. in: JCI | PubMed | Google Scholar |

1Division of Immunobiology, Cincinnati Children's Hospital Medical Center, Cincinnati, United States of America

2Division of Nephrology and Hypertension, Cincinnati Children's Hospital Medical Center, Cincinnati, United States of America

3Division of Biomedical Informatics, Cincinnati Children's Hospital Medical Center, Cincinnati, United States of America

4Department of Chemistry and Biochemistry and the Harper Cancer Research Ins, University of Notre Dame, South Bend, United States of America

5Division of Rheumatology, Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, United States of America

6Department of Pathology and Laboratory Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, United States of America

7Immunology Disease Area, Novartis Institutes for BioMedical Research, Basel, Switzerland

8Division of Nephrology and Hypertension, Department of Internal Medicine, University of Cincinnati College of Medicine, Cincinnati, United States of America

9Division of Transplantation, Department of Surgery, University of Cincinnati College of Medicine, Cincinnati, United States of America

10Department of Chemistry and Biochemistry and the Harper Cancer Research Ins, University of Notre Dame, Notre Dame, United States of America

Find articles by Wieczorek, G. in: JCI | PubMed | Google Scholar |

1Division of Immunobiology, Cincinnati Children's Hospital Medical Center, Cincinnati, United States of America

2Division of Nephrology and Hypertension, Cincinnati Children's Hospital Medical Center, Cincinnati, United States of America

3Division of Biomedical Informatics, Cincinnati Children's Hospital Medical Center, Cincinnati, United States of America

4Department of Chemistry and Biochemistry and the Harper Cancer Research Ins, University of Notre Dame, South Bend, United States of America

5Division of Rheumatology, Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, United States of America

6Department of Pathology and Laboratory Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, United States of America

7Immunology Disease Area, Novartis Institutes for BioMedical Research, Basel, Switzerland

8Division of Nephrology and Hypertension, Department of Internal Medicine, University of Cincinnati College of Medicine, Cincinnati, United States of America

9Division of Transplantation, Department of Surgery, University of Cincinnati College of Medicine, Cincinnati, United States of America

10Department of Chemistry and Biochemistry and the Harper Cancer Research Ins, University of Notre Dame, Notre Dame, United States of America

Find articles by Alloway, R. in: JCI | PubMed | Google Scholar |

1Division of Immunobiology, Cincinnati Children's Hospital Medical Center, Cincinnati, United States of America

2Division of Nephrology and Hypertension, Cincinnati Children's Hospital Medical Center, Cincinnati, United States of America

3Division of Biomedical Informatics, Cincinnati Children's Hospital Medical Center, Cincinnati, United States of America

4Department of Chemistry and Biochemistry and the Harper Cancer Research Ins, University of Notre Dame, South Bend, United States of America

5Division of Rheumatology, Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, United States of America

6Department of Pathology and Laboratory Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, United States of America

7Immunology Disease Area, Novartis Institutes for BioMedical Research, Basel, Switzerland

8Division of Nephrology and Hypertension, Department of Internal Medicine, University of Cincinnati College of Medicine, Cincinnati, United States of America

9Division of Transplantation, Department of Surgery, University of Cincinnati College of Medicine, Cincinnati, United States of America

10Department of Chemistry and Biochemistry and the Harper Cancer Research Ins, University of Notre Dame, Notre Dame, United States of America

Find articles by Shields, A. in: JCI | PubMed | Google Scholar

1Division of Immunobiology, Cincinnati Children's Hospital Medical Center, Cincinnati, United States of America

2Division of Nephrology and Hypertension, Cincinnati Children's Hospital Medical Center, Cincinnati, United States of America

3Division of Biomedical Informatics, Cincinnati Children's Hospital Medical Center, Cincinnati, United States of America

4Department of Chemistry and Biochemistry and the Harper Cancer Research Ins, University of Notre Dame, South Bend, United States of America

5Division of Rheumatology, Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, United States of America

6Department of Pathology and Laboratory Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, United States of America

7Immunology Disease Area, Novartis Institutes for BioMedical Research, Basel, Switzerland

8Division of Nephrology and Hypertension, Department of Internal Medicine, University of Cincinnati College of Medicine, Cincinnati, United States of America

9Division of Transplantation, Department of Surgery, University of Cincinnati College of Medicine, Cincinnati, United States of America

10Department of Chemistry and Biochemistry and the Harper Cancer Research Ins, University of Notre Dame, Notre Dame, United States of America

Find articles by Baker, B. in: JCI | PubMed | Google Scholar |

1Division of Immunobiology, Cincinnati Children's Hospital Medical Center, Cincinnati, United States of America

2Division of Nephrology and Hypertension, Cincinnati Children's Hospital Medical Center, Cincinnati, United States of America

3Division of Biomedical Informatics, Cincinnati Children's Hospital Medical Center, Cincinnati, United States of America

4Department of Chemistry and Biochemistry and the Harper Cancer Research Ins, University of Notre Dame, South Bend, United States of America

5Division of Rheumatology, Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, United States of America

6Department of Pathology and Laboratory Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, United States of America

7Immunology Disease Area, Novartis Institutes for BioMedical Research, Basel, Switzerland

8Division of Nephrology and Hypertension, Department of Internal Medicine, University of Cincinnati College of Medicine, Cincinnati, United States of America

9Division of Transplantation, Department of Surgery, University of Cincinnati College of Medicine, Cincinnati, United States of America

10Department of Chemistry and Biochemistry and the Harper Cancer Research Ins, University of Notre Dame, Notre Dame, United States of America

Find articles by Woodle, E. in: JCI | PubMed | Google Scholar

1Division of Immunobiology, Cincinnati Children's Hospital Medical Center, Cincinnati, United States of America

2Division of Nephrology and Hypertension, Cincinnati Children's Hospital Medical Center, Cincinnati, United States of America

3Division of Biomedical Informatics, Cincinnati Children's Hospital Medical Center, Cincinnati, United States of America

4Department of Chemistry and Biochemistry and the Harper Cancer Research Ins, University of Notre Dame, South Bend, United States of America

5Division of Rheumatology, Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, United States of America

6Department of Pathology and Laboratory Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, United States of America

7Immunology Disease Area, Novartis Institutes for BioMedical Research, Basel, Switzerland

8Division of Nephrology and Hypertension, Department of Internal Medicine, University of Cincinnati College of Medicine, Cincinnati, United States of America

9Division of Transplantation, Department of Surgery, University of Cincinnati College of Medicine, Cincinnati, United States of America

10Department of Chemistry and Biochemistry and the Harper Cancer Research Ins, University of Notre Dame, Notre Dame, United States of America

Find articles by Hildeman, D. in: JCI | PubMed | Google Scholar |

Published May 25, 2023 - More info

J Clin Invest. https://doi.org/10.1172/JCI170191.
Copyright © 2023, Shi et al. This work is licensed under the Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
Published May 25, 2023 - Version history
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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 TCRα/β sequencing on rBx from patients with ACR under differing IS: tacrolimus, iscalimab, and belatacept. We found distinct CD8+ T cell phenotypes (e.g., effector, memory, exhausted) depending upon IS type, particularly within clonally expanded cells (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 TCRα/β cDNAs from CD8EXP into Jurkat76 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 anti-rejection 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 to improve detection, assessment, and treatment of rejection.

Graphical Abstract
graphical abstract
Supplemental material

View Differential gene expression lists between clusters found in figure 1 (supplemental figure 1), figure 2 (supplemental figure 2), figure 3 (supplemental figure 3), figure 5(supplemental table 4), figure 6 (supplemental table 5), figure 7 (supplemental table 6), and figure 9 (supplemental table 7).

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Version history
  • Version 1 (May 25, 2023): In-Press Preview
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