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

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Author

  • 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
Show all

Summary, in English

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.

Publishing year

2015

Language

English

Publication/Series

eLife

Volume

2015

Issue

4

Document type

Journal article

Publisher

eLife Sciences Publications

Topic

  • Immunology in the medical area

Status

Published

ISBN/ISSN/Other

  • ISSN: 2050-084X