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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...

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Autores principales: Kim, Joseph Y., Lei, Zhengdeng, Maienschein-Cline, Mark, Chlipala, George E., Balamurugan, Arumugam, McDiarmid, Sue V., Azari, Kodi, Yang, Otto O.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Lippincott Williams & Wilkins 2021
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.
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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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