CD8(+) T cells specific to caspase-cleaved antigens derived from apoptotic T cells represent a principal player in chronic immune activation (CIA). Here, we found that both apoptotic epitope (AE)-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 (c)HCV infection. However, AE-specific CD8(+) T cells produced tumor necrosis factor (TNF)-α and interleukin-2 at the intrahepatic level significantly more than HCV-specific CD8(+) T cells, despite both populations acquiring high levels of programmed death-1 receptor expression. Contextually, only AE-specific CD8(+) T cells correlated with both interferon-stimulated gene levels in T cells and hepatic fibrosis score. Taken together, these data suggest that AE-specific CD8(+) T cells can sustain CIA by their capacity to produce TNF-α and be resistant to inhibitory signals more than HCV-specific CD8(+) T cells in cHCV 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 NELSON; 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. - ELETTRONICO. - .:.(2015), pp. jiv460-jiv460. [10.1093/infdis/jiv460]

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 NELSON;CALVO, LUDOVICA;DI FILIPPO, SIMONA;VULLO, Vincenzo;BARNABA, Vincenzo
2015

Abstract

CD8(+) T cells specific to caspase-cleaved antigens derived from apoptotic T cells represent a principal player in chronic immune activation (CIA). Here, we found that both apoptotic epitope (AE)-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 (c)HCV infection. However, AE-specific CD8(+) T cells produced tumor necrosis factor (TNF)-α and interleukin-2 at the intrahepatic level significantly more than HCV-specific CD8(+) T cells, despite both populations acquiring high levels of programmed death-1 receptor expression. Contextually, only AE-specific CD8(+) T cells correlated with both interferon-stimulated gene levels in T cells and hepatic fibrosis score. Taken together, these data suggest that AE-specific CD8(+) T cells can sustain CIA by their capacity to produce TNF-α and be resistant to inhibitory signals more than HCV-specific CD8(+) T cells in cHCV infection.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/793154
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