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T cell unresponsiveness in a pediatric cystic fibrosis patient: a case report

A girl was diagnosed with cystic fibrosis (CF) at birth, with repeatedly positive sweat tests and homozygous F508del mutations of her CF transmembrane conductance regulator (CFTR) gene. From an early age, her lung disease was more severe than her birth cohort peers despite aggressive treatment. At t...

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Autores principales: Kushwah, Rahul, Gagnon, Stéphane, Sweezey, Neil B
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3896844/
https://www.ncbi.nlm.nih.gov/pubmed/24438707
http://dx.doi.org/10.1186/1710-1492-10-2
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author Kushwah, Rahul
Gagnon, Stéphane
Sweezey, Neil B
author_facet Kushwah, Rahul
Gagnon, Stéphane
Sweezey, Neil B
author_sort Kushwah, Rahul
collection PubMed
description A girl was diagnosed with cystic fibrosis (CF) at birth, with repeatedly positive sweat tests and homozygous F508del mutations of her CF transmembrane conductance regulator (CFTR) gene. From an early age, her lung disease was more severe than her birth cohort peers despite aggressive treatment. At the age of 16 she was listed for lung transplantation, but prior to transplant was not on systemic corticosteroids or other immunosuppressive agents. In response to ex vivo stimulation, her pre-transplant peripheral blood T cells unexpectedly failed to produce detectable levels of IFN-γ, unlike cells from healthy controls or from another girl with CF and lung disease of comparable severity. Furthermore, naïve T cells freshly isolated from her peripheral blood showed a complete block of T cell differentiation into Th1, Th17 and Treg lineages, even in the presence of cytokines known to promote differentiation into the respective lineages. Her serology has been remarkably devoid of evidence of exposure to viruses that have been associated with T cell exhaustion. However, her freshly isolated naïve T cells showed sustained expression of markers of T cell exhaustion, which were further induced upon ex vivo stimulation, pointing to T cell exhaustion as the cause of the failure of naïve T cells to undergo differentiation in response to cytokine stimulation. Although excessive inflammation in CF lung can be both ineffective at clearing certain pathogens as well as destructive to the lung tissue itself, adequate inflammation is a component of an effective overall immune response to microbial pathogens. Our present findings suggest that intrinsic impairment of T cell differentiation may have contributed to the greater severity and more rapid progression of her CF lung disease than of the lung disease of most of her peers.
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spelling pubmed-38968442014-01-22 T cell unresponsiveness in a pediatric cystic fibrosis patient: a case report Kushwah, Rahul Gagnon, Stéphane Sweezey, Neil B Allergy Asthma Clin Immunol Case Report A girl was diagnosed with cystic fibrosis (CF) at birth, with repeatedly positive sweat tests and homozygous F508del mutations of her CF transmembrane conductance regulator (CFTR) gene. From an early age, her lung disease was more severe than her birth cohort peers despite aggressive treatment. At the age of 16 she was listed for lung transplantation, but prior to transplant was not on systemic corticosteroids or other immunosuppressive agents. In response to ex vivo stimulation, her pre-transplant peripheral blood T cells unexpectedly failed to produce detectable levels of IFN-γ, unlike cells from healthy controls or from another girl with CF and lung disease of comparable severity. Furthermore, naïve T cells freshly isolated from her peripheral blood showed a complete block of T cell differentiation into Th1, Th17 and Treg lineages, even in the presence of cytokines known to promote differentiation into the respective lineages. Her serology has been remarkably devoid of evidence of exposure to viruses that have been associated with T cell exhaustion. However, her freshly isolated naïve T cells showed sustained expression of markers of T cell exhaustion, which were further induced upon ex vivo stimulation, pointing to T cell exhaustion as the cause of the failure of naïve T cells to undergo differentiation in response to cytokine stimulation. Although excessive inflammation in CF lung can be both ineffective at clearing certain pathogens as well as destructive to the lung tissue itself, adequate inflammation is a component of an effective overall immune response to microbial pathogens. Our present findings suggest that intrinsic impairment of T cell differentiation may have contributed to the greater severity and more rapid progression of her CF lung disease than of the lung disease of most of her peers. BioMed Central 2014-01-17 /pmc/articles/PMC3896844/ /pubmed/24438707 http://dx.doi.org/10.1186/1710-1492-10-2 Text en Copyright © 2014 Kushwah et al.; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Case Report
Kushwah, Rahul
Gagnon, Stéphane
Sweezey, Neil B
T cell unresponsiveness in a pediatric cystic fibrosis patient: a case report
title T cell unresponsiveness in a pediatric cystic fibrosis patient: a case report
title_full T cell unresponsiveness in a pediatric cystic fibrosis patient: a case report
title_fullStr T cell unresponsiveness in a pediatric cystic fibrosis patient: a case report
title_full_unstemmed T cell unresponsiveness in a pediatric cystic fibrosis patient: a case report
title_short T cell unresponsiveness in a pediatric cystic fibrosis patient: a case report
title_sort t cell unresponsiveness in a pediatric cystic fibrosis patient: a case report
topic Case Report
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3896844/
https://www.ncbi.nlm.nih.gov/pubmed/24438707
http://dx.doi.org/10.1186/1710-1492-10-2
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