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

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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

Edité par CCSD ; eLife Sciences Publication -

International audience. 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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