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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 and van Buuren, Marit M, et al. (2015) In eLife 2015(4).
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,... (More)
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. (Less)
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eLife
volume
2015
issue
4
publisher
eLife Sciences Publications LTD.
external identifiers
  • pmid:26568315
  • scopus:84952814441
  • wos:000373442500001
ISSN
2050-084X
DOI
10.7554/eLife.07916
language
English
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yes
id
da3aa51b-78c1-4d13-adfe-22d04e54604e (old id 8235492)
date added to LUP
2016-02-26 14:32:07
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2017-09-24 04:09:13
@article{da3aa51b-78c1-4d13-adfe-22d04e54604e,
  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.},
  author       = {Alanio, Cécile and Nicoli, Francesco and Sultanik, Philippe and Flecken, Tobias and Perot, Brieuc and Duffy, Darragh and Bianchi, Elisabetta and Lim, Annick and Clave, Emmanuel and van Buuren, Marit M and Schnuriger, Aurélie and Johnsson, Kerstin and Boussier, Jeremy and Garbarg-Chenon, Antoine and Bousquet, Laurence and Mottez, Estelle and Schumacher, Ton N and Toubert, Antoine and Appay, Victor and Heshmati, Farhad and Thimme, Robert and Pol, Stanislas and Mallet, Vincent and Albert, Matthew L},
  issn         = {2050-084X},
  language     = {eng},
  number       = {4},
  publisher    = {eLife Sciences Publications LTD.},
  series       = {eLife},
  title        = {Bystander hyperactivation of preimmune CD8(+) T cells in chronic HCV patients},
  url          = {http://dx.doi.org/10.7554/eLife.07916},
  volume       = {2015},
  year         = {2015},
}