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Protection against Bronchiolitis Obliterans Syndrome Is Associated with Allograft CCR7(+)CD45RA(−) T Regulatory Cells

Bronchiolitis obliterans syndrome (BOS) is the major obstacle to long-term survival after lung transplantation, yet markers for early detection and intervention are currently lacking. Given the role of regulatory T cells (Treg) in modulation of immunity, we hypothesized that frequencies of Treg in b...

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Autores principales: Gregson, Aric L., Hoji, Aki, Palchevskiy, Vyacheslav, Hu, Scott, Weigt, S. Samuel, Liao, Eileen, Derhovanessian, Ariss, Saggar, Rajeev, Song, Sophie, Elashoff, Robert, Yang, Otto O., Belperio, John A.
Formato: Texto
Lenguaje:English
Publicado: Public Library of Science 2010
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2894051/
https://www.ncbi.nlm.nih.gov/pubmed/20613873
http://dx.doi.org/10.1371/journal.pone.0011354
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author Gregson, Aric L.
Hoji, Aki
Palchevskiy, Vyacheslav
Hu, Scott
Weigt, S. Samuel
Liao, Eileen
Derhovanessian, Ariss
Saggar, Rajeev
Song, Sophie
Elashoff, Robert
Yang, Otto O.
Belperio, John A.
author_facet Gregson, Aric L.
Hoji, Aki
Palchevskiy, Vyacheslav
Hu, Scott
Weigt, S. Samuel
Liao, Eileen
Derhovanessian, Ariss
Saggar, Rajeev
Song, Sophie
Elashoff, Robert
Yang, Otto O.
Belperio, John A.
author_sort Gregson, Aric L.
collection PubMed
description Bronchiolitis obliterans syndrome (BOS) is the major obstacle to long-term survival after lung transplantation, yet markers for early detection and intervention are currently lacking. Given the role of regulatory T cells (Treg) in modulation of immunity, we hypothesized that frequencies of Treg in bronchoalveolar lavage fluid (BALF) after lung transplantation would predict subsequent development of BOS. Seventy BALF specimens obtained from 47 lung transplant recipients were analyzed for Treg lymphocyte subsets by flow cytometry, in parallel with ELISA measurements of chemokines. Allograft biopsy tissue was stained for chemokines of interest. Treg were essentially all CD45RA(−), and total Treg frequency did not correlate to BOS outcome. The majority of Treg were CCR4(+) and CD103(−) and neither of these subsets correlated to risk for BOS. In contrast, higher percentages of CCR7(+) Treg correlated to reduced risk of BOS. Additionally, the CCR7 ligand CCL21 correlated with CCR7(+) Treg frequency and inversely with BOS. Higher frequencies of CCR7(+) CD3(+)CD4(+)CD25(hi)Foxp3(+)CD45RA(−) lymphocytes in lung allografts is associated with protection against subsequent development of BOS, suggesting that this subset of putative Treg may down-modulate alloimmunity. CCL21 may be pivotal for the recruitment of this distinct subset to the lung allograft and thereby decrease the risk for chronic rejection.
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spelling pubmed-28940512010-07-07 Protection against Bronchiolitis Obliterans Syndrome Is Associated with Allograft CCR7(+)CD45RA(−) T Regulatory Cells Gregson, Aric L. Hoji, Aki Palchevskiy, Vyacheslav Hu, Scott Weigt, S. Samuel Liao, Eileen Derhovanessian, Ariss Saggar, Rajeev Song, Sophie Elashoff, Robert Yang, Otto O. Belperio, John A. PLoS One Research Article Bronchiolitis obliterans syndrome (BOS) is the major obstacle to long-term survival after lung transplantation, yet markers for early detection and intervention are currently lacking. Given the role of regulatory T cells (Treg) in modulation of immunity, we hypothesized that frequencies of Treg in bronchoalveolar lavage fluid (BALF) after lung transplantation would predict subsequent development of BOS. Seventy BALF specimens obtained from 47 lung transplant recipients were analyzed for Treg lymphocyte subsets by flow cytometry, in parallel with ELISA measurements of chemokines. Allograft biopsy tissue was stained for chemokines of interest. Treg were essentially all CD45RA(−), and total Treg frequency did not correlate to BOS outcome. The majority of Treg were CCR4(+) and CD103(−) and neither of these subsets correlated to risk for BOS. In contrast, higher percentages of CCR7(+) Treg correlated to reduced risk of BOS. Additionally, the CCR7 ligand CCL21 correlated with CCR7(+) Treg frequency and inversely with BOS. Higher frequencies of CCR7(+) CD3(+)CD4(+)CD25(hi)Foxp3(+)CD45RA(−) lymphocytes in lung allografts is associated with protection against subsequent development of BOS, suggesting that this subset of putative Treg may down-modulate alloimmunity. CCL21 may be pivotal for the recruitment of this distinct subset to the lung allograft and thereby decrease the risk for chronic rejection. Public Library of Science 2010-06-29 /pmc/articles/PMC2894051/ /pubmed/20613873 http://dx.doi.org/10.1371/journal.pone.0011354 Text en Gregson et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Gregson, Aric L.
Hoji, Aki
Palchevskiy, Vyacheslav
Hu, Scott
Weigt, S. Samuel
Liao, Eileen
Derhovanessian, Ariss
Saggar, Rajeev
Song, Sophie
Elashoff, Robert
Yang, Otto O.
Belperio, John A.
Protection against Bronchiolitis Obliterans Syndrome Is Associated with Allograft CCR7(+)CD45RA(−) T Regulatory Cells
title Protection against Bronchiolitis Obliterans Syndrome Is Associated with Allograft CCR7(+)CD45RA(−) T Regulatory Cells
title_full Protection against Bronchiolitis Obliterans Syndrome Is Associated with Allograft CCR7(+)CD45RA(−) T Regulatory Cells
title_fullStr Protection against Bronchiolitis Obliterans Syndrome Is Associated with Allograft CCR7(+)CD45RA(−) T Regulatory Cells
title_full_unstemmed Protection against Bronchiolitis Obliterans Syndrome Is Associated with Allograft CCR7(+)CD45RA(−) T Regulatory Cells
title_short Protection against Bronchiolitis Obliterans Syndrome Is Associated with Allograft CCR7(+)CD45RA(−) T Regulatory Cells
title_sort protection against bronchiolitis obliterans syndrome is associated with allograft ccr7(+)cd45ra(−) t regulatory cells
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2894051/
https://www.ncbi.nlm.nih.gov/pubmed/20613873
http://dx.doi.org/10.1371/journal.pone.0011354
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