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.
Apoptotic epitope-specific CD8+ T cells and interferon signaling intersect in chronic Hepatitis C virus infection / 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. - In: THE JOURNAL OF INFECTIOUS DISEASES. - ISSN 0022-1899. - STAMPA. - 213:(2016), pp. 674-683. [10.1093/infdis/jiv460]
Apoptotic epitope-specific CD8+ T cells and interferon signaling intersect in chronic Hepatitis C virus infection
Grazi Gian Luca;
2016
Abstract
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.File | Dimensione | Formato | |
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