Bystander hyperactivation of preimmune CD8+ T cells in chronic HCV patients. - Sorbonne Université Access content directly
Journal Articles eLife Year : 2015

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

Elisabetta Bianchi
Antoine Toubert
Farhad Heshmati
  • Function : Author
Stanislas Pol
Vincent Mallet

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.
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hal-01306801 , version 1 (25-04-2016)

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Cécile Alanio, Francesco Nicoli, Philippe Sultanik, Tobias Flecken, Brieuc Perot, et al.. Bystander hyperactivation of preimmune CD8+ T cells in chronic HCV patients.. eLife, 2015, 4, pp.e07916. ⟨10.7554/eLife.07916⟩. ⟨hal-01306801⟩
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