Impact of age and telomere length on circulating T cells and rejection risk after lung transplantation for idiopathic pulmonary fibrosis
Copyright © 2023 International Society for the Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved..
BACKGROUND: Most idiopathic pulmonary fibrosis (IPF) lung transplant recipients (IPF-LTRs) have short telomere (ST) length. Inherited mutations in telomere-related genes are associated with the development of T cell immunodeficiency. Despite this, IPF-LTRs with telomere-related rare variants are not protected from acute cellular rejection (ACR). We set out to determine the impact of both age and telomere length on the circulating T cell compartment and ACR burden of IPF-LTRs.
METHODS: We identified 106 IPF-LTRs who had telomere length testing using flowFISH (57 with short telomeres and 49 with long telomeres) as well as a subset from both cohorts who had cryopreserved PBMC at least 1 time point, 6 months posttransplantation. Circulating T cells from before transplantation and at 6 and 12 months posttransplantation were analyzed using multiparameter flow cytometry to study phenotype and functional capacity, and bulk T cell receptor sequencing was performed to study repertoire diversity. Linear regression was used to study the relationship of age and telomere length on early (within 1 year) and late (between 1 and 2 years) ACR.
RESULTS: IPF-LTRs with ST were found to have premature "aging" of their circulating T cell compartment, with age-agnostic elevations in posttransplant terminal differentiation of CD8+ T cells, increased granzyme B positivity of both CD8+ and CD4+ T cells, upregulation of the exhaustion marker, CD57, and chemotactic protein CCR5, and enhanced T cell receptor clonal expansion. Additionally, we found a significant decline in early ACR burden with increasing age, but only in the ST cohort.
CONCLUSIONS: IPF-LTRs with ST have premature "aging" of their circulating T cell compartment posttransplantation and a clear age-related decline in ACR burden.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:42 |
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| Enthalten in: |
The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation - 42(2023), 12 vom: 01. Dez., Seite 1666-1677 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Snyder, Mark E [VerfasserIn] |
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| Links: |
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| Themen: |
Aging |
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| Anmerkungen: |
Date Completed 13.11.2023 Date Revised 18.02.2024 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.healun.2023.08.001 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM360441408 |
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| 100 | 1 | |a Snyder, Mark E |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Impact of age and telomere length on circulating T cells and rejection risk after lung transplantation for idiopathic pulmonary fibrosis |
| 264 | 1 | |c 2023 | |
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| 500 | |a Date Completed 13.11.2023 | ||
| 500 | |a Date Revised 18.02.2024 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2023 International Society for the Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved. | ||
| 520 | |a BACKGROUND: Most idiopathic pulmonary fibrosis (IPF) lung transplant recipients (IPF-LTRs) have short telomere (ST) length. Inherited mutations in telomere-related genes are associated with the development of T cell immunodeficiency. Despite this, IPF-LTRs with telomere-related rare variants are not protected from acute cellular rejection (ACR). We set out to determine the impact of both age and telomere length on the circulating T cell compartment and ACR burden of IPF-LTRs | ||
| 520 | |a METHODS: We identified 106 IPF-LTRs who had telomere length testing using flowFISH (57 with short telomeres and 49 with long telomeres) as well as a subset from both cohorts who had cryopreserved PBMC at least 1 time point, 6 months posttransplantation. Circulating T cells from before transplantation and at 6 and 12 months posttransplantation were analyzed using multiparameter flow cytometry to study phenotype and functional capacity, and bulk T cell receptor sequencing was performed to study repertoire diversity. Linear regression was used to study the relationship of age and telomere length on early (within 1 year) and late (between 1 and 2 years) ACR | ||
| 520 | |a RESULTS: IPF-LTRs with ST were found to have premature "aging" of their circulating T cell compartment, with age-agnostic elevations in posttransplant terminal differentiation of CD8+ T cells, increased granzyme B positivity of both CD8+ and CD4+ T cells, upregulation of the exhaustion marker, CD57, and chemotactic protein CCR5, and enhanced T cell receptor clonal expansion. Additionally, we found a significant decline in early ACR burden with increasing age, but only in the ST cohort | ||
| 520 | |a CONCLUSIONS: IPF-LTRs with ST have premature "aging" of their circulating T cell compartment posttransplantation and a clear age-related decline in ACR burden | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, N.I.H., Extramural | |
| 650 | 4 | |a T cells | |
| 650 | 4 | |a aging | |
| 650 | 4 | |a lung transplantation | |
| 650 | 4 | |a rejection | |
| 650 | 4 | |a telomere length | |
| 650 | 7 | |a Receptors, Antigen, T-Cell |2 NLM | |
| 700 | 1 | |a Anderson, Michaela R |e verfasserin |4 aut | |
| 700 | 1 | |a Benvenuto, Luke J |e verfasserin |4 aut | |
| 700 | 1 | |a Sutton, Rachel M |e verfasserin |4 aut | |
| 700 | 1 | |a Bondonese, Anna |e verfasserin |4 aut | |
| 700 | 1 | |a Koshy, Ritchie |e verfasserin |4 aut | |
| 700 | 1 | |a Burke, Robin |e verfasserin |4 aut | |
| 700 | 1 | |a Clifford, Sarah |e verfasserin |4 aut | |
| 700 | 1 | |a Craig, Andrew |e verfasserin |4 aut | |
| 700 | 1 | |a Iasella, Carlo J |e verfasserin |4 aut | |
| 700 | 1 | |a Hannan, Stefanie J |e verfasserin |4 aut | |
| 700 | 1 | |a Popescu, Iulia |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Yingze |e verfasserin |4 aut | |
| 700 | 1 | |a Sanchez, Pablo G |e verfasserin |4 aut | |
| 700 | 1 | |a Alder, Jonathan K |e verfasserin |4 aut | |
| 700 | 1 | |a McDyer, John F |e verfasserin |4 aut | |
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