Apoptotic Epitope–Specific CD8+T Cells and Interferon Signaling Intersect in Chronic Hepatitis C Virus Infection

CD8+ T cells specific to caspase-cleaved antigens derived from apoptotic T cells represent a principal player in chronic immune activation. Here, we found that both apoptotic epitope–specific and hepatitis C virus (HCV)–specific CD8+ T cells were mostly confined within the effector memory (EM) or te...

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Published in:The Journal of infectious diseases 2016-02, Vol.213 (4), p.674-683
Main Authors: Martini, Helene, Citro, Alessandra, Martire, Carmela, D'Ettorre, Gabriella, Labbadia, Giancarlo, Accapezzato, Daniele, Piconese, Silvia, De Marzio, Paolo, Cavallari, Eugenio N., Calvo, Ludovica, Rizzo, Fabiana, Severa, Martina, Coccia, Eliana M., Grazi, Gian Luca, Di Filippo, Simona, Sidney, John, Vullo, Vincenzo, Sette, Alessandro, Barnaba, Vincenzo
Format: Article
Language:English
Subjects:
Adult
Aged
Apoptosis
CD8-Positive T-Lymphocytes - immunology
Female
Hepatitis C, Chronic - immunology
Hepatitis C, Chronic - pathology
Humans
Interferons - metabolism
Interleukin-2 - secretion
Liver Cirrhosis - pathology
Male
Middle Aged
PATHOGENESIS AND HOST RESPONSE
Signal Transduction
T-Lymphocyte Subsets - immunology
Tumor Necrosis Factor-alpha - secretion
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Summary:CD8+ T cells specific to caspase-cleaved antigens derived from apoptotic T cells represent a principal player in chronic immune activation. Here, we found that both apoptotic epitope–specific and hepatitis C virus (HCV)–specific CD8+ T cells were mostly confined within the effector memory (EM) or terminally differentiated EM CD45RA+ cell subsets expressing a dysfunctional T-helper 1–like signature program in chronic HCV infection. However, apoptotic epitope–specific CD8+ T cells produced tumor necrosis factor α and interleukin 2 at the intrahepatic level significantly more than HCV-specific CD8+ T cells, despite both populations expressing high levels of programmed death 1 receptor. Contextually, only apoptotic epitope–specific CD8+ T cells correlated with both interferon-stimulated gene levels in T cells and hepatic fibrosis score. Together, these data suggest that, compared with HCV-specific CD8+ T cells, apoptotic epitope–specific CD8+ T cells can better sustain chronic immune activation, owing to their capacity to produce tumor necrosis factor α, and exhibit greater resistance to inhibitory signals during chronic HCV infection.
ISSN:0022-1899
1537-6613
DOI:10.1093/infdis/jiv460