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Bystander hyperactivation of preimmune CD8(+) T cells in chronic HCV patients

Chronic infection perturbs immune homeostasis. While prior studies have reported dysregulation of effector and memory cells, little is known about the effects on naïve T cell populations. We performed a cross-sectional study of chronic hepatitis C (cHCV) patients using tetramer-associated magnetic e...

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Autores principales: Alanio, Cécile, Nicoli, Francesco, Sultanik, Philippe, Flecken, Tobias, Perot, Brieuc, Duffy, Darragh, Bianchi, Elisabetta, Lim, Annick, Clave, Emmanuel, van Buuren, Marit M, Schnuriger, Aurélie, Johnsson, Kerstin, Boussier, Jeremy, Garbarg-Chenon, Antoine, Bousquet, Laurence, Mottez, Estelle, Schumacher, Ton N, Toubert, Antoine, Appay, Victor, Heshmati, Farhad, Thimme, Robert, Pol, Stanislas, Mallet, Vincent, Albert, Matthew L
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4752008/
https://www.ncbi.nlm.nih.gov/pubmed/26568315
http://dx.doi.org/10.7554/eLife.07916
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author Alanio, Cécile
Nicoli, Francesco
Sultanik, Philippe
Flecken, Tobias
Perot, Brieuc
Duffy, Darragh
Bianchi, Elisabetta
Lim, Annick
Clave, Emmanuel
van Buuren, Marit M
Schnuriger, Aurélie
Johnsson, Kerstin
Boussier, Jeremy
Garbarg-Chenon, Antoine
Bousquet, Laurence
Mottez, Estelle
Schumacher, Ton N
Toubert, Antoine
Appay, Victor
Heshmati, Farhad
Thimme, Robert
Pol, Stanislas
Mallet, Vincent
Albert, Matthew L
author_facet Alanio, Cécile
Nicoli, Francesco
Sultanik, Philippe
Flecken, Tobias
Perot, Brieuc
Duffy, Darragh
Bianchi, Elisabetta
Lim, Annick
Clave, Emmanuel
van Buuren, Marit M
Schnuriger, Aurélie
Johnsson, Kerstin
Boussier, Jeremy
Garbarg-Chenon, Antoine
Bousquet, Laurence
Mottez, Estelle
Schumacher, Ton N
Toubert, Antoine
Appay, Victor
Heshmati, Farhad
Thimme, Robert
Pol, Stanislas
Mallet, Vincent
Albert, Matthew L
author_sort Alanio, Cécile
collection PubMed
description Chronic infection perturbs immune homeostasis. While prior studies have reported dysregulation of effector and memory cells, little is known about the effects on naïve T cell populations. We performed a cross-sectional study of chronic hepatitis C (cHCV) patients using tetramer-associated magnetic enrichment to study antigen-specific inexperienced CD8(+) T cells (i.e., tumor or unrelated virus-specific populations in tumor-free and sero-negative individuals). cHCV showed normal precursor frequencies, but increased proportions of memory-phenotype inexperienced cells, as compared to healthy donors or cured HCV patients. These observations could be explained by low surface expression of CD5, a negative regulator of TCR signaling. Accordingly, we demonstrated TCR hyperactivation and generation of potent CD8(+) T cell responses from the altered T cell repertoire of cHCV patients. In sum, we provide the first evidence that naïve CD8(+) T cells are dysregulated during cHCV infection, and establish a new mechanism of immune perturbation secondary to chronic infection. DOI: http://dx.doi.org/10.7554/eLife.07916.001
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spelling pubmed-47520082016-02-16 Bystander hyperactivation of preimmune CD8(+) T cells in chronic HCV patients Alanio, Cécile Nicoli, Francesco Sultanik, Philippe Flecken, Tobias Perot, Brieuc Duffy, Darragh Bianchi, Elisabetta Lim, Annick Clave, Emmanuel van Buuren, Marit M Schnuriger, Aurélie Johnsson, Kerstin Boussier, Jeremy Garbarg-Chenon, Antoine Bousquet, Laurence Mottez, Estelle Schumacher, Ton N Toubert, Antoine Appay, Victor Heshmati, Farhad Thimme, Robert Pol, Stanislas Mallet, Vincent Albert, Matthew L eLife Human Biology and Medicine Chronic infection perturbs immune homeostasis. While prior studies have reported dysregulation of effector and memory cells, little is known about the effects on naïve T cell populations. We performed a cross-sectional study of chronic hepatitis C (cHCV) patients using tetramer-associated magnetic enrichment to study antigen-specific inexperienced CD8(+) T cells (i.e., tumor or unrelated virus-specific populations in tumor-free and sero-negative individuals). cHCV showed normal precursor frequencies, but increased proportions of memory-phenotype inexperienced cells, as compared to healthy donors or cured HCV patients. These observations could be explained by low surface expression of CD5, a negative regulator of TCR signaling. Accordingly, we demonstrated TCR hyperactivation and generation of potent CD8(+) T cell responses from the altered T cell repertoire of cHCV patients. In sum, we provide the first evidence that naïve CD8(+) T cells are dysregulated during cHCV infection, and establish a new mechanism of immune perturbation secondary to chronic infection. DOI: http://dx.doi.org/10.7554/eLife.07916.001 eLife Sciences Publications, Ltd 2015-11-14 /pmc/articles/PMC4752008/ /pubmed/26568315 http://dx.doi.org/10.7554/eLife.07916 Text en © 2015, Alanio et al http://creativecommons.org/licenses/by/4.0/ This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited.
spellingShingle Human Biology and Medicine
Alanio, Cécile
Nicoli, Francesco
Sultanik, Philippe
Flecken, Tobias
Perot, Brieuc
Duffy, Darragh
Bianchi, Elisabetta
Lim, Annick
Clave, Emmanuel
van Buuren, Marit M
Schnuriger, Aurélie
Johnsson, Kerstin
Boussier, Jeremy
Garbarg-Chenon, Antoine
Bousquet, Laurence
Mottez, Estelle
Schumacher, Ton N
Toubert, Antoine
Appay, Victor
Heshmati, Farhad
Thimme, Robert
Pol, Stanislas
Mallet, Vincent
Albert, Matthew L
Bystander hyperactivation of preimmune CD8(+) T cells in chronic HCV patients
title Bystander hyperactivation of preimmune CD8(+) T cells in chronic HCV patients
title_full Bystander hyperactivation of preimmune CD8(+) T cells in chronic HCV patients
title_fullStr Bystander hyperactivation of preimmune CD8(+) T cells in chronic HCV patients
title_full_unstemmed Bystander hyperactivation of preimmune CD8(+) T cells in chronic HCV patients
title_short Bystander hyperactivation of preimmune CD8(+) T cells in chronic HCV patients
title_sort bystander hyperactivation of preimmune cd8(+) t cells in chronic hcv patients
topic Human Biology and Medicine
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4752008/
https://www.ncbi.nlm.nih.gov/pubmed/26568315
http://dx.doi.org/10.7554/eLife.07916
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