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

• Published in: eLife 2015-11, Vol.4 (4)
• Main Authors: Alanio, Cécile, Nicoli, Francesco, Sultanik, Philippe, Flecken, Tobias, Perot, Brieuc, Duffy, Darragh, Bianchi, Elisabetta, Lim, Annick, Clave, Emmanuel, van Buuren, Marit M, Schnuriger, Aurélie, Johnsson, Kerstin, Boussier, Jeremy, Garbarg-Chenon, Antoine, Bousquet, Laurence, Mottez, Estelle, Schumacher, Ton N, Toubert, Antoine, Appay, Victor, Heshmati, Farhad, Thimme, Robert, Pol, Stanislas, Mallet, Vincent, Albert, Matthew L
• Format: Article
• Language: English
• Subjects: Basic Medicine; CD5 Antigens - metabolism; CD8 T cell dysfunction; CD8-Positive T-Lymphocytes - immunology; chronic inflammation; Cross-Sectional Studies; Hepacivirus - immunology; Hepatitis C, Chronic - pathology; Human Biology and Medicine; Human health and pathology; Humans; Immunologi inom det medicinska området; Immunology; Immunology in the medical area; Life Sciences; Lymphocyte Activation; Lymphocytes T; Medical and Health Sciences; Medicin och hälsovetenskap; Medicinska och farmaceutiska grundvetenskaper; Pre-immune repertoire; Receptors, Antigen, T-Cell - metabolism; Signal Transduction; TCR signaling; viral immunology
• ISSN: 2050-084X; 2050-084X
• DOI: 10.7554/eLife.07916

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.