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

Autor: 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
Jazyk: angličtina
Rok vydání: 2015
Předmět:
Zdroj: eLife, Vol 4 (2015)
Druh dokumentu: article
ISSN: 2050-084X
DOI: 10.7554/eLife.07916
Popis: 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.
Databáze: Directory of Open Access Journals