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

Cécile Alanio; Francesco Nicoli; Philippe Sultanik; Tobias Flecken; Brieuc Perot; Darragh Duffy; Elisabetta Bianchi; Annick Lim; Emmanuel Clave; Marit M van Buuren; Aurélie Schnuriger; Kerstin Johnsson; Jeremy Boussier; Antoine Garbarg-Chenon; Laurence Bousquet; Estelle Mottez; Ton N Schumacher; Antoine Toubert; Victor Appay; Farhad Heshmati; Robert Thimme; Stanislas Pol; Vincent Mallet; Matthew L Albert

doi:10.7554/eLife.07916

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

Cécile Alanio, Francesco Nicoli, Philippe Sultanik, Tobias Flecken, Brieuc Perot, Darragh Duffy, Elisabetta Bianchi, Annick Lim, Emmanuel Clave, Marit M van Buuren, Aurélie Schnuriger, Kerstin Johnsson, Jeremy Boussier, Antoine Garbarg-Chenon, Laurence Bousquet, Estelle Mottez, Ton N Schumacher, Antoine Toubert, Victor Appay, Farhad HeshmatiRobert Thimme, Stanislas Pol, Vincent Mallet, Matthew L Albert

Mathematics (Faculty of Engineering)

Research output: Contribution to journal › Article › peer-review

Abstract

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.

Original language	English
Journal	eLife
Volume	2015
Issue number	4
DOIs	https://doi.org/10.7554/eLife.07916
Publication status	Published - 2015

Subject classification (UKÄ)

Immunology in the Medical Area (including Cell and Immunotherapy)

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.7554/eLife.07916

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Alanio, C., Nicoli, F., Sultanik, P., Flecken, T., Perot, B., Duffy, D., Bianchi, E., Lim, A., Clave, E., van Buuren, M. M., Schnuriger, A., Johnsson, K., Boussier, J., Garbarg-Chenon, A., Bousquet, L., Mottez, E., Schumacher, T. N., Toubert, A., Appay, V., ... Albert, M. L. (2015). Bystander hyperactivation of preimmune CD8(+) T cells in chronic HCV patients. eLife, 2015(4). https://doi.org/10.7554/eLife.07916

@article{da3aa51b78c14d13adfe22d04e54604e,

title = "Bystander hyperactivation of preimmune CD8(+) T cells in chronic HCV patients",

abstract = "Chronic infection perturbs immune homeostasis. While prior studies have reported dysregulation of effector and memory cells, little is known about the effects on na{\"i}ve 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 na{\"i}ve CD8(+) T cells are dysregulated during cHCV infection, and establish a new mechanism of immune perturbation secondary to chronic infection.",

author = "C{\'e}cile Alanio and Francesco Nicoli and Philippe Sultanik and Tobias Flecken and Brieuc Perot and Darragh Duffy and Elisabetta Bianchi and Annick Lim and Emmanuel Clave and {van Buuren}, {Marit M} and Aur{\'e}lie Schnuriger and Kerstin Johnsson and Jeremy Boussier and Antoine Garbarg-Chenon and Laurence Bousquet and Estelle Mottez and Schumacher, {Ton N} and Antoine Toubert and Victor Appay and Farhad Heshmati and Robert Thimme and Stanislas Pol and Vincent Mallet and Albert, {Matthew L}",

year = "2015",

doi = "10.7554/eLife.07916",

language = "English",

volume = "2015",

journal = "eLife",

issn = "2050-084X",

publisher = "eLife Sciences Publications",

number = "4",

}

Alanio, C, Nicoli, F, Sultanik, P, Flecken, T, Perot, B, Duffy, D, Bianchi, E, Lim, A, Clave, E, van Buuren, MM, Schnuriger, A, Johnsson, K, Boussier, J, Garbarg-Chenon, A, Bousquet, L, Mottez, E, Schumacher, TN, Toubert, A, Appay, V, Heshmati, F, Thimme, R, Pol, S, Mallet, V & Albert, ML 2015, 'Bystander hyperactivation of preimmune CD8(+) T cells in chronic HCV patients', eLife, vol. 2015, no. 4. https://doi.org/10.7554/eLife.07916

TY - JOUR

T1 - Bystander hyperactivation of preimmune CD8(+) T cells in chronic HCV patients

AU - Alanio, Cécile

AU - Nicoli, Francesco

AU - Sultanik, Philippe

AU - Flecken, Tobias

AU - Perot, Brieuc

AU - Duffy, Darragh

AU - Bianchi, Elisabetta

AU - Lim, Annick

AU - Clave, Emmanuel

AU - van Buuren, Marit M

AU - Schnuriger, Aurélie

AU - Johnsson, Kerstin

AU - Boussier, Jeremy

AU - Garbarg-Chenon, Antoine

AU - Bousquet, Laurence

AU - Mottez, Estelle

AU - Schumacher, Ton N

AU - Toubert, Antoine

AU - Appay, Victor

AU - Heshmati, Farhad

AU - Thimme, Robert

AU - Pol, Stanislas

AU - Mallet, Vincent

AU - Albert, Matthew L

PY - 2015

Y1 - 2015

N2 - 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.

AB - 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.

U2 - 10.7554/eLife.07916

DO - 10.7554/eLife.07916

M3 - Article

C2 - 26568315

SN - 2050-084X

VL - 2015

JO - eLife

JF - eLife

IS - 4

ER -

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

Abstract

Subject classification (UKÄ)

UN SDGs

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