Affordable Access

deepdyve-link
Publisher Website

Longitudinal Analysis of the T-cell Receptor Repertoire in Graft-infiltrating Lymphocytes Following Hand Transplantation.

Authors
  • Kim, Joseph Y1
  • Lei, Zhengdeng2
  • Maienschein-Cline, Mark2
  • Chlipala, George E2
  • Balamurugan, Arumugam3
  • McDiarmid, Sue V4, 5
  • Azari, Kodi5, 6
  • Yang, Otto O3, 7
  • 1 Division of Infectious Diseases, Department of Medicine, University of Illinois College of Medicine Peoria, Peoria, IL.
  • 2 Research Informatics Core, Research Resources Center, University of Illinois at Chicago, Chicago, IL.
  • 3 Division of Infectious Diseases, Department of Medicine, Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA.
  • 4 Department of Pediatrics, Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA.
  • 5 Department of Surgery, Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA.
  • 6 Department of Orthopaedic Surgery, Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA.
  • 7 Department of Microbiology, Immunology, and Molecular Genetics, Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA.
Type
Published Article
Journal
Transplantation
Publication Date
Jul 01, 2021
Volume
105
Issue
7
Pages
1502–1509
Identifiers
DOI: 10.1097/TP.0000000000003535
PMID: 33208695
Source
Medline
Language
English
License
Unknown

Abstract

T lymphocyte-mediated acute rejection is a significant complication following solid organ transplantation. Standard methods of monitoring for acute rejection rely on assessing histological tissue damage but do not define the immunopathogenesis. Additionally, current therapies for rejection broadly blunt cellular immunity, creating a high risk for opportunistic infections. There is, therefore, a need to better understand the process of acute cellular rejection to help develop improved prognostic tests and narrowly targeted therapies. Through next-generation sequencing, we characterized and compared the clonal T-cell receptor (TCR) repertoires of graft-infiltrating lymphocytes (GILs) and blood-derived lymphocytes from a hand transplant recipient over 420 days following transplantation. We also tracked the TCR clonal persistence and V beta (BV) gene usage, evaluating overlap between these 2 compartments. TCR repertoires of blood and GIL populations remained distinct throughout the sampling period, and differential BV usage was consistently seen between these compartments. GIL TCR clones persisted over time and were seen in only limited frequency in the blood T-lymphocyte populations. We demonstrate that blood monitoring of TCR clones does not reveal the pathogenic process of acute cellular rejection in transplanted tissue. GILs show clonal persistence with biased BV usage, suggesting that tissue TCR clonal monitoring could be useful, although a deeper understanding is necessary to prognosticate rejection based on TCR clonal repertoires. Finally, the distinct TCR BV usage bias in GILs raises the possibility for prevention and therapy of acute cellular rejection based on targeting of specific TCR clones. Copyright © 2020 The Author(s). Published by Wolters Kluwer Health, Inc.

Report this publication

Statistics

Seen <100 times