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Longitudinal Analysis of the T-cell Receptor Repertoire in Graft-infiltrating Lymphocytes Following Hand Transplantation
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 b...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Lippincott Williams & Wilkins
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8221714/ https://www.ncbi.nlm.nih.gov/pubmed/33208695 http://dx.doi.org/10.1097/TP.0000000000003535 |
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author | Kim, Joseph Y. Lei, Zhengdeng Maienschein-Cline, Mark Chlipala, George E. Balamurugan, Arumugam McDiarmid, Sue V. Azari, Kodi Yang, Otto O. |
author_facet | Kim, Joseph Y. Lei, Zhengdeng Maienschein-Cline, Mark Chlipala, George E. Balamurugan, Arumugam McDiarmid, Sue V. Azari, Kodi Yang, Otto O. |
author_sort | Kim, Joseph Y. |
collection | PubMed |
description | 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. METHODS. 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. RESULTS. 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. CONCLUSIONS. 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. |
format | Online Article Text |
id | pubmed-8221714 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Lippincott Williams & Wilkins |
record_format | MEDLINE/PubMed |
spelling | pubmed-82217142021-06-24 Longitudinal Analysis of the T-cell Receptor Repertoire in Graft-infiltrating Lymphocytes Following Hand Transplantation Kim, Joseph Y. Lei, Zhengdeng Maienschein-Cline, Mark Chlipala, George E. Balamurugan, Arumugam McDiarmid, Sue V. Azari, Kodi Yang, Otto O. Transplantation Original Basic Science—General 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. METHODS. 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. RESULTS. 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. CONCLUSIONS. 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. Lippincott Williams & Wilkins 2021-06-23 2021-07 /pmc/articles/PMC8221714/ /pubmed/33208695 http://dx.doi.org/10.1097/TP.0000000000003535 Text en Copyright © 2020 The Author(s). Published by Wolters Kluwer Health, Inc. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND) (https://creativecommons.org/licenses/by-nc-nd/4.0/) , where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. |
spellingShingle | Original Basic Science—General Kim, Joseph Y. Lei, Zhengdeng Maienschein-Cline, Mark Chlipala, George E. Balamurugan, Arumugam McDiarmid, Sue V. Azari, Kodi Yang, Otto O. Longitudinal Analysis of the T-cell Receptor Repertoire in Graft-infiltrating Lymphocytes Following Hand Transplantation |
title | Longitudinal Analysis of the T-cell Receptor Repertoire in Graft-infiltrating Lymphocytes Following Hand Transplantation |
title_full | Longitudinal Analysis of the T-cell Receptor Repertoire in Graft-infiltrating Lymphocytes Following Hand Transplantation |
title_fullStr | Longitudinal Analysis of the T-cell Receptor Repertoire in Graft-infiltrating Lymphocytes Following Hand Transplantation |
title_full_unstemmed | Longitudinal Analysis of the T-cell Receptor Repertoire in Graft-infiltrating Lymphocytes Following Hand Transplantation |
title_short | Longitudinal Analysis of the T-cell Receptor Repertoire in Graft-infiltrating Lymphocytes Following Hand Transplantation |
title_sort | longitudinal analysis of the t-cell receptor repertoire in graft-infiltrating lymphocytes following hand transplantation |
topic | Original Basic Science—General |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8221714/ https://www.ncbi.nlm.nih.gov/pubmed/33208695 http://dx.doi.org/10.1097/TP.0000000000003535 |
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