1. Bystander hyperactivation of preimmune CD8+ T cells in chronic HCV patients.
- Author
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Sultanik, Philippe, Perot, Brieuc, Alanio, Cécile, Duffy, Darragh, Boussier, Jeremy, Albert, Matthew L., Schnuriger, Aurélie, Garbarg-Chenon, Antoine, Johnsson, Kerstin, Bousquet, Laurence, Pol, Stanislas, Mallet, Vincent, Heshmati, Farhad, Mottez, Estelle, Nicoli, Francesco, Appay, Victor, Flecken, Tobias, Thimme, Robert, Bianchi, Elisabetta, and Lim, Annick
- Subjects
CHRONIC hepatitis C ,ADULT T-cell leukemia ,PHENOTYPES - 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. [ABSTRACT FROM AUTHOR]- Published
- 2015
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